1.
Jmol
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Jmol is computer software for molecular modelling chemical structures in 3-dimensions. Jmol returns a 3D representation of a molecule that may be used as a teaching tool and it is written in the programming language Java, so it can run on the operating systems Windows, macOS, Linux, and Unix, if Java is installed. It is free and open-source software released under a GNU Lesser General Public License version 2.0, a standalone application and a software development kit exist that can be integrated into other Java applications, such as Bioclipse and Taverna. A popular feature is an applet that can be integrated into web pages to display molecules in a variety of ways, for example, molecules can be displayed as ball-and-stick models, space-filling models, ribbon diagrams, etc. Jmol supports a range of chemical file formats, including Protein Data Bank, Crystallographic Information File, MDL Molfile. There is also a JavaScript-only version, JSmol, that can be used on computers with no Java, the Jmol applet, among other abilities, offers an alternative to the Chime plug-in, which is no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS9. Jmol requires Java installation and operates on a variety of platforms. For example, Jmol is fully functional in Mozilla Firefox, Internet Explorer, Opera, Google Chrome, fast and Scriptable Molecular Graphics in Web Browsers without Java3D
2.
ChEMBL
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ChEMBL or ChEMBLdb is a manually curated chemical database of bioactive molecules with drug-like properties. It is maintained by the European Bioinformatics Institute, of the European Molecular Biology Laboratory, based at the Wellcome Trust Genome Campus, Hinxton, the database, originally known as StARlite, was developed by a biotechnology company called Inpharmatica Ltd. later acquired by Galapagos NV. The data was acquired for EMBL in 2008 with an award from The Wellcome Trust, resulting in the creation of the ChEMBL chemogenomics group at EMBL-EBI, the ChEMBL database contains compound bioactivity data against drug targets. Bioactivity is reported in Ki, Kd, IC50, and EC50, data can be filtered and analyzed to develop compound screening libraries for lead identification during drug discovery. ChEMBL version 2 was launched in January 2010, including 2.4 million bioassay measurements covering 622,824 compounds and this was obtained from curating over 34,000 publications across twelve medicinal chemistry journals. ChEMBLs coverage of available bioactivity data has grown to become the most comprehensive ever seen in a public database, in October 2010 ChEMBL version 8 was launched, with over 2.97 million bioassay measurements covering 636,269 compounds. ChEMBL_10 saw the addition of the PubChem confirmatory assays, in order to integrate data that is comparable to the type, ChEMBLdb can be accessed via a web interface or downloaded by File Transfer Protocol. It is formatted in a manner amenable to computerized data mining, ChEMBL is also integrated into other large-scale chemistry resources, including PubChem and the ChemSpider system of the Royal Society of Chemistry. In addition to the database, the ChEMBL group have developed tools and these include Kinase SARfari, an integrated chemogenomics workbench focussed on kinases. The system incorporates and links sequence, structure, compounds and screening data, the primary purpose of ChEMBL-NTD is to provide a freely accessible and permanent archive and distribution centre for deposited data. July 2012 saw the release of a new data service, sponsored by the Medicines for Malaria Venture. The data in this service includes compounds from the Malaria Box screening set, myChEMBL, the ChEMBL virtual machine, was released in October 2013 to allow users to access a complete and free, easy-to-install cheminformatics infrastructure. In December 2013, the operations of the SureChem patent informatics database were transferred to EMBL-EBI, in a portmanteau, SureChem was renamed SureChEMBL. 2014 saw the introduction of the new resource ADME SARfari - a tool for predicting and comparing cross-species ADME targets
3.
ChemSpider
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ChemSpider is a database of chemicals. ChemSpider is owned by the Royal Society of Chemistry, the database contains information on more than 50 million molecules from over 500 data sources including, Each chemical is given a unique identifier, which forms part of a corresponding URL. This is an approach to develop an online chemistry database. The search can be used to widen or restrict already found results, structure searching on mobile devices can be done using free apps for iOS and for the Android. The ChemSpider database has been used in combination with text mining as the basis of document markup. The result is a system between chemistry documents and information look-up via ChemSpider into over 150 data sources. ChemSpider was acquired by the Royal Society of Chemistry in May,2009, prior to the acquisition by RSC, ChemSpider was controlled by a private corporation, ChemZoo Inc. The system was first launched in March 2007 in a release form. ChemSpider has expanded the generic support of a database to include support of the Wikipedia chemical structure collection via their WiChempedia implementation. A number of services are available online. SyntheticPages is an interactive database of synthetic chemistry procedures operated by the Royal Society of Chemistry. Users submit synthetic procedures which they have conducted themselves for publication on the site and these procedures may be original works, but they are more often based on literature reactions. Citations to the published procedure are made where appropriate. They are checked by an editor before posting. The pages do not undergo formal peer-review like a journal article. The comments are moderated by scientific editors. The intention is to collect practical experience of how to conduct useful chemical synthesis in the lab, while experimental methods published in an ordinary academic journal are listed formally and concisely, the procedures in ChemSpider SyntheticPages are given with more practical detail. Comments by submitters are included as well, other publications with comparable amounts of detail include Organic Syntheses and Inorganic Syntheses
4.
DrugBank
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The DrugBank database is a comprehensive, freely accessible, online database containing information on drugs and drug targets. As both a bioinformatics and a resource, DrugBank combines detailed drug data with comprehensive drug target information. Because of its scope, comprehensive referencing and unusually detailed data descriptions. As a result, links to DrugBank are maintained for nearly all drugs listed in Wikipedia, DrugBank is widely used by the drug industry, medicinal chemists, pharmacists, physicians, students and the general public. Its extensive drug and drug-target data has enabled the discovery and repurposing of a number of existing drugs to treat rare, the latest release of the database contains 8227 drug entries including 2003 FDA-approved small molecule drugs,221 FDA-approved biotech drugs,93 nutraceuticals and over 6000 experimental drugs. Additionally,4270 non-redundant protein sequences are linked to these drug entries, each DrugCard entry contains more than 200 data fields with half of the information being devoted to drug/chemical data and the other half devoted to drug target or protein data. Four additional databases, HMDB, T3DB, SMPDB and FooDB are also part of a suite of metabolomic/cheminformatic databases. The first version of DrugBank was released in 2006 and this early release contained relatively modest information about 841 FDA-approved small molecule drugs and 113 biotech drugs. It also included information on 2133 drug targets, the second version of DrugBank was released in 2009. This greatly expanded and improved version of the database included 1344 approved small molecule drugs and 123 biotech drugs as well as 3037 unique drug targets. Version 2.0 also included, for the first time, withdrawn drugs and illicit drugs, version 3.0 was released in 2011. This version contained 1424 approved small molecule drugs and 132 biotech drugs as well as >4000 unique drug targets, version 3.0 also included drug transporter data, drug pathway data, drug pricing, patent and manufacturing data as well as data on >5000 experimental drugs. Version 4.0 was released in 2014 and this version included 1558 FDA-approved small molecule drugs,155 biotech drugs and 4200 unique drug targets. Version 4.0 also incorporated information on drug metabolites, drug taxonomy, drug spectra, drug binding constants. Table 1 provides a complete statistical summary of the history of DrugBank’s development. All data in DrugBank is non-proprietary or is derived from a non-proprietary source and it is freely accessible and available to anyone. In addition, nearly every item is fully traceable and explicitly referenced to the original source. DrugBank data is available through a web interface and downloads
5.
IUPHAR/BPS
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The IUPHAR/BPS Guide to PHARMACOLOGY is an open-access website, acting as a portal to information on the biological targets of licensed drugs and other small molecules. The Guide to PHARMACOLOGY is developed as a joint venture between the International Union of Basic and Clinical Pharmacology and the British Pharmacological Society and this replaces and expands upon the original 2009 IUPHAR Database. The information featured includes pharmacological data, target and gene nomenclature, overviews and commentaries on each target family are included, with links to key references. The Guide to PHARMACOLOGY was initially made available online in December 2011 with additional material released in July 2012 and its network of over 700 specialist advisors contribute expertise and data. The current PI and Grant holder of the GtoPdb project is Prof. Jamie A. Davies, the development and release of the first version of the GtoPdb in 2012 was described in an editorial published in the British Journal of Pharmacology entitled Guide to Pharmacology. org- an update. The IUPHAR-DB is no longer being developed and all the contained within this site is now available through the Guide to PHARMACOLOGY. A complete list of all the approved drugs included on the website is available via the ligand list. The Guide to PHARMACOLOGY is being expanded to include information on targets and ligands. Search features on the website include quick and advanced search options, other features include Hot topic news items and a recent receptor-ligand pairing list. A hard copy summary of the database is published as The Concise Guide to Pharmacology 2015/2016 as a series of papers as a bi-annual supplement to the British Journal of Pharmacology. The Guide to PHARMACOLOGY includes links to other relevant resources via target, many of these resources maintain reciprocal links with the relevant Guide to PHARMACOLOGY pages. As of November 2015 the Wellcome Trust is supporting a new project to develop the Guide to Immumopharmacology, the latter continues to be supported by the British Pharmacological Society
6.
PubChem
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PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information, a component of the National Library of Medicine, PubChem can be accessed for free through a web user interface. Millions of compound structures and descriptive datasets can be downloaded via FTP. PubChem contains substance descriptions and small molecules with fewer than 1000 atoms and 1000 bonds, more than 80 database vendors contribute to the growing PubChem database. PubChem consists of three dynamically growing primary databases, as of 28 January 2016, Compounds,82.6 million entries, contains pure and characterized chemical compounds. Substances,198 million entries, contains also mixtures, extracts, complexes, bioAssay, bioactivity results from 1.1 million high-throughput screening programs with several million values. PubChem contains its own online molecule editor with SMILES/SMARTS and InChI support that allows the import and export of all common chemical file formats to search for structures and fragments. In the text search form the database fields can be searched by adding the name in square brackets to the search term. A numeric range is represented by two separated by a colon. The search terms and field names are case-insensitive, parentheses and the logical operators AND, OR, and NOT can be used. AND is assumed if no operator is used, example,0,5000,50,10 -5,5 PubChem was released in 2004. The American Chemical Society has raised concerns about the publicly supported PubChem database and they have a strong interest in the issue since the Chemical Abstracts Service generates a large percentage of the societys revenue. To advocate their position against the PubChem database, ACS has actively lobbied the US Congress, soon after PubChems creation, the American Chemical Society lobbied U. S. Congress to restrict the operation of PubChem, which they asserted competes with their Chemical Abstracts Service
7.
International Chemical Identifier
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Initially developed by IUPAC and NIST from 2000 to 2005, the format and algorithms are non-proprietary. The continuing development of the standard has supported since 2010 by the not-for-profit InChI Trust. The current version is 1.04 and was released in September 2011, prior to 1.04, the software was freely available under the open source LGPL license, but it now uses a custom license called IUPAC-InChI Trust License. Not all layers have to be provided, for instance, the layer can be omitted if that type of information is not relevant to the particular application. InChIs can thus be seen as akin to a general and extremely formalized version of IUPAC names and they can express more information than the simpler SMILES notation and differ in that every structure has a unique InChI string, which is important in database applications. Information about the 3-dimensional coordinates of atoms is not represented in InChI, the InChI algorithm converts input structural information into a unique InChI identifier in a three-step process, normalization, canonicalization, and serialization. The InChIKey, sometimes referred to as a hashed InChI, is a fixed length condensed digital representation of the InChI that is not human-understandable. The InChIKey specification was released in September 2007 in order to facilitate web searches for chemical compounds and it should be noted that, unlike the InChI, the InChIKey is not unique, though collisions can be calculated to be very rare, they happen. In January 2009 the final 1.02 version of the InChI software was released and this provided a means to generate so called standard InChI, which does not allow for user selectable options in dealing with the stereochemistry and tautomeric layers of the InChI string. The standard InChIKey is then the hashed version of the standard InChI string, the standard InChI will simplify comparison of InChI strings and keys generated by different groups, and subsequently accessed via diverse sources such as databases and web resources. Every InChI starts with the string InChI= followed by the version number and this is followed by the letter S for standard InChIs. The remaining information is structured as a sequence of layers and sub-layers, the layers and sub-layers are separated by the delimiter / and start with a characteristic prefix letter. The six layers with important sublayers are, Main layer Chemical formula and this is the only sublayer that must occur in every InChI. The atoms in the formula are numbered in sequence, this sublayer describes which atoms are connected by bonds to which other ones. Describes how many hydrogen atoms are connected to each of the other atoms, the condensed,27 character standard InChIKey is a hashed version of the full standard InChI, designed to allow for easy web searches of chemical compounds. Most chemical structures on the Web up to 2007 have been represented as GIF files, the full InChI turned out to be too lengthy for easy searching, and therefore the InChIKey was developed. With all databases currently having below 50 million structures, such duplication appears unlikely at present, a recent study more extensively studies the collision rate finding that the experimental collision rate is in agreement with the theoretical expectations. Example, Morphine has the structure shown on the right, as the InChI cannot be reconstructed from the InChIKey, an InChIKey always needs to be linked to the original InChI to get back to the original structure
8.
Simplified molecular-input line-entry system
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The simplified molecular-input line-entry system is a specification in form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules, the original SMILES specification was initiated in the 1980s. It has since modified and extended. In 2007, a standard called OpenSMILES was developed in the open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. The Environmental Protection Agency funded the project to develop SMILES. It has since modified and extended by others, most notably by Daylight Chemical Information Systems. In 2007, a standard called OpenSMILES was developed by the Blue Obelisk open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, in July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is generally considered to have the advantage of being slightly more human-readable than InChI, the term SMILES refers to a line notation for encoding molecular structures and specific instances should strictly be called SMILES strings. However, the term SMILES is also used to refer to both a single SMILES string and a number of SMILES strings, the exact meaning is usually apparent from the context. The terms canonical and isomeric can lead to confusion when applied to SMILES. The terms describe different attributes of SMILES strings and are not mutually exclusive, typically, a number of equally valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol, algorithms have been developed to generate the same SMILES string for a given molecule, of the many possible strings, these algorithms choose only one of them. This SMILES is unique for each structure, although dependent on the algorithm used to generate it. These algorithms first convert the SMILES to a representation of the molecular structure. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database, there is currently no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, and these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES
9.
Chemical formula
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These are limited to a single typographic line of symbols, which may include subscripts and superscripts. A chemical formula is not a name, and it contains no words. Although a chemical formula may imply certain simple chemical structures, it is not the same as a full chemical structural formula. Chemical formulas can fully specify the structure of only the simplest of molecules and chemical substances, the simplest types of chemical formulas are called empirical formulas, which use letters and numbers indicating the numerical proportions of atoms of each type. Molecular formulas indicate the numbers of each type of atom in a molecule. For example, the formula for glucose is CH2O, while its molecular formula is C6H12O6. This is possible if the relevant bonding is easy to show in one dimension, an example is the condensed molecular/chemical formula for ethanol, which is CH3-CH2-OH or CH3CH2OH. For reasons of structural complexity, there is no condensed chemical formula that specifies glucose, chemical formulas may be used in chemical equations to describe chemical reactions and other chemical transformations, such as the dissolving of ionic compounds into solution. A chemical formula identifies each constituent element by its chemical symbol, in empirical formulas, these proportions begin with a key element and then assign numbers of atoms of the other elements in the compound, as ratios to the key element. For molecular compounds, these numbers can all be expressed as whole numbers. For example, the formula of ethanol may be written C2H6O because the molecules of ethanol all contain two carbon atoms, six hydrogen atoms, and one oxygen atom. Some types of compounds, however, cannot be written with entirely whole-number empirical formulas. An example is boron carbide, whose formula of CBn is a variable non-whole number ratio with n ranging from over 4 to more than 6.5. When the chemical compound of the consists of simple molecules. These types of formulas are known as molecular formulas and condensed formulas. A molecular formula enumerates the number of atoms to reflect those in the molecule, so that the formula for glucose is C6H12O6 rather than the glucose empirical formula. However, except for very simple substances, molecular chemical formulas lack needed structural information, for simple molecules, a condensed formula is a type of chemical formula that may fully imply a correct structural formula. For example, ethanol may be represented by the chemical formula CH3CH2OH
10.
Melting point
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The melting point of a solid is the temperature at which it changes state from solid to liquid at atmospheric pressure. At the melting point the solid and liquid phase exist in equilibrium, the melting point of a substance depends on pressure and is usually specified at standard pressure. When considered as the temperature of the change from liquid to solid. Because of the ability of some substances to supercool, the point is not considered as a characteristic property of a substance. For most substances, melting and freezing points are approximately equal, for example, the melting point and freezing point of mercury is 234.32 kelvins. However, certain substances possess differing solid-liquid transition temperatures, for example, agar melts at 85 °C and solidifies from 31 °C to 40 °C, such direction dependence is known as hysteresis. The melting point of ice at 1 atmosphere of pressure is close to 0 °C. In the presence of nucleating substances the freezing point of water is the same as the melting point, the chemical element with the highest melting point is tungsten, at 3687 K, this property makes tungsten excellent for use as filaments in light bulbs. Many laboratory techniques exist for the determination of melting points, a Kofler bench is a metal strip with a temperature gradient. Any substance can be placed on a section of the strip revealing its thermal behaviour at the temperature at that point, differential scanning calorimetry gives information on melting point together with its enthalpy of fusion. A basic melting point apparatus for the analysis of crystalline solids consists of an oil bath with a transparent window, the several grains of a solid are placed in a thin glass tube and partially immersed in the oil bath. The oil bath is heated and with the aid of the melting of the individual crystals at a certain temperature can be observed. In large/small devices, the sample is placed in a heating block, the measurement can also be made continuously with an operating process. For instance, oil refineries measure the point of diesel fuel online, meaning that the sample is taken from the process. This allows for more frequent measurements as the sample does not have to be manually collected, for refractory materials the extremely high melting point may be determined by heating the material in a black body furnace and measuring the black-body temperature with an optical pyrometer. For the highest melting materials, this may require extrapolation by several hundred degrees, the spectral radiance from an incandescent body is known to be a function of its temperature. An optical pyrometer matches the radiance of a body under study to the radiance of a source that has been previously calibrated as a function of temperature, in this way, the measurement of the absolute magnitude of the intensity of radiation is unnecessary. However, known temperatures must be used to determine the calibration of the pyrometer, for temperatures above the calibration range of the source, an extrapolation technique must be employed
11.
Psychedelic drug
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A psychedelic drug is a drug whose primary action is to alter cognition and perception, typically by agonising serotonin receptors. The psychedelic experience is often compared to forms of consciousness such as trance, meditation, yoga, religious ecstasy, dreaming. With a few exceptions, most psychedelic drugs fall into one of the three following families of compounds, tryptamines, phenethylamines, and lysergamides. Many psychedelic drugs are illegal worldwide under the UN conventions unless used in a medical or religious context, despite these regulations, recreational use of psychedelics is common. The word was coined in 1956 by British psychiatrist, Humphry Osmond, the spelling loathed by American ethnobotanist, Richard Schultes, aldous Huxley had suggested to Humphry Osmond in 1956 his own coinage phanerothyme. Recently, the term entheogenic has come into use to denote the use of drugs in a religious/spiritual/mystical context. Psychedelics have a history of traditional use in medicine and religion. In this context, they are known as entheogens. Native American practitioners using mescaline-containing cacti have reported success against alcoholism, ayahuasca, which contains the powerful psychedelic DMT, is used in Peru and other parts of South America for spiritual and physical healing as well as in religious festivals. Classical or serotonergic psychedelics include LSD, psilocin, mescaline, and this class of psychedelics includes the classical hallucinogens, including the lysergamides like LSD and LSA, tryptamines like psilocybin and DMT, and phenethylamines like mescaline and 2C-B. Many of these psychedelics cause remarkably similar effects, despite their different chemical structure, however, many users report that the three families have subjectively different qualities in the feel of the experience, which are difficult to describe. At lower doses, these include sensory alterations, such as the warping of surfaces, shape suggestibility, users often report intense colors that they have not previously experienced, and repetitive geometric shapes are common. Higher doses often cause intense and fundamental alterations of sensory perception, some compounds, such as 2C-B, have extremely tight dose curves, meaning the difference between a non-event and an overwhelming disconnection from reality can be very slight. There can be substantial differences between the drugs, however. The empathogen-entactogens are phenethylamines of the MDxx class such as MDMA, MDEA and their effects are characterized by feelings of openness, euphoria, empathy, love, heightened self-awareness, and by mild audio and visual distortions. Their adoption by the subculture is probably due to the enhancement of the overall social and musical experience. Certain dissociative drugs acting via NMDA antagonism are known to produce what some might consider psychedelic effects, the main differences between dissociative psychedelics and serotonergic hallucinogens are that the dissociatives cause more intense derealization and depersonalization. For example, ketamine produces sensations of being disconnected from ones body, salvia divinorum is a dissociative that is sometimes classified as an atypical psychedelic
12.
Substituted amphetamine
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The compounds in this class span a variety of pharmacological subclasses, including stimulants, empathogens, and hallucinogens, among others. Some of amphetamines substituted derivatives occur in nature, for example in the leaves of Ephedra and these have been used since antiquity for their pharmacological effects. Amphetamine was first produced at the end of the 19th century, by the 1930s, amphetamine and some of its derivative compounds found use as decongestants in the symptomatic treatment of colds and also occasionally as psychoactive agents. Their effects on the nervous system are diverse, but can be summarized by three overlapping types of activity, psychoanaleptic, hallucinogenic and empathogenic. Various substituted amphetamines may cause these actions either separately or in combination, amphetamines are a subgroup of the substituted phenethylamine class of compounds. Substitution of hydrogen results in a large class of compounds. Natives of Yemen and Ethiopia have a tradition of chewing khat leaves to achieve a stimulating effect. The active substances of khat are cathinone and, to a lesser extent, amphetamine was first synthesized in 1887 by Romanian chemist Lazăr Edeleanu, although its pharmacological effects remained unknown until the 1930s. MDMA was produced in 1912 as an intermediate product, however, this synthesis also went largely unnoticed. In the 1920s, both methamphetamine and the dextrorotatory optical isomer of amphetamine, dextroamphetamine, were synthesized and this synthesis was a by-product of a search for ephedrine, a bronchodilator used to treat asthma extracted exclusively from natural sources. Over-the-counter use of substituted amphetamines was initiated in the early 1930s by the pharmaceutical company Smith, Kline & French, as a medicine for colds and nasal congestion. Subsequently, amphetamine was used in the treatment of narcolepsy, obesity, hay fever, orthostatic hypotension, epilepsy, Parkinsons disease, alcoholism, the reinforcing effects of substituted amphetamines were quickly discovered, and the misuse of substituted amphetamines had been noted as far back as 1936. During World War II, amphetamines were used by the German military to keep their tank crews awake for long periods and it was noticed that extended rest was required after such artificially induced activity. The widespread use of substituted amphetamines began in postwar Japan and quickly spread to other countries, modified designer amphetamines gained popularity since the 1960s, such as MDA and PMA. In 1970, the United States adopted the Controlled Substances Act that limited non-medical use of substituted amphetamines, street use of PMA was noted in 1972. MDMA emerged as a substitute to MDA in the early 1970s, american chemist Alexander Shulgin first synthesized the drug in 1976 and through him the drug was briefly introduced into psychotherapy. Recreational use grew and in 1985 MDMA was banned by the US authorities in an emergency scheduling initiated by the Drug Enforcement Administration, since the mid-1990s, MDMA has become a popular entactogenic drug among the youth and quite often non-MDMA substances were sold as ecstasy. Ongoing trials are investigating its efficacy as an adjunct to psychotherapy in the management of treatment-resistant post-traumatic stress disorder
13.
Substituted phenethylamine
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The structural formula of any substituted phenethylamine contains a phenyl ring that is joined to an amino group via an ethyl sidechain. Hence, any substituted phenethylamine can be classified according to the substitution of hydrogen atoms on phenethylamines phenyl ring, sidechain, numerous endogenous compounds – including hormones, monoamine neurotransmitters, and many trace amines – are substituted phenethylamines. Several notable recreational drugs, such as MDMA, methamphetamine, all of the substituted amphetamines and substituted methylenedioxyphenethylamines are substituted phenethylamines as well. Substituted amphetamines Substituted methylenedioxyphenethylamines Substituted cathinones Substituted phenylmorpholines 2Cs and DOx Substituted tryptamines
14.
Alexander Shulgin
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Alexander Theodore Sasha Shulgin was an American medicinal chemist, biochemist, organic chemist, pharmacologist, psychopharmacologist, and author. In 1991 and 1997, he and his wife Ann Shulgin authored the books PIHKAL and TIHKAL, Shulgin performed seminal work into the descriptive synthesis of many of these compounds. Some of Shulgins noteworthy discoveries include compounds of the 2C* family, due in part to Shulgins extensive work in the field of psychedelic research and the rational drug design of psychedelic drugs, he has since been dubbed the godfather of psychedelics. Shulgin was born in Berkeley, California to Theodore Stevens Shulgin and his father was born in Russia, while his mother was born in Illinois. Both Theodore and Henrietta were public school teachers in Alameda County, Shulgin began studying organic chemistry as a Harvard University scholarship student at the age of 16. In 1943 he dropped out of school to join the U. S. Navy, while serving on USS Pope in the Navy during World War II, Shulgin was given a glass of orange juice by a nurse prior to surgery for a thumb infection. Shulgin drank the juice and, assuming that the powder at the bottom of the glass was a sedative, upon waking he learned that the powder was undissolved sugar. The experience made him aware of the influence of placebos over the human mind, after serving in the Navy, Shulgin returned to Berkeley, California, and in 1954 earned his Ph. D. in biochemistry from the University of California, Berkeley. Through the late 1950s Shulgin completed post-doctoral work in the fields of psychiatry and pharmacology at University of California, after working at Bio-Rad Laboratories as a research director for a brief period, he began work at Dow Chemical Company as a senior research chemist. At this time he had a series of experiences that helped to shape his further goals and research. I first explored mescaline in the late 50s, I learned there was a great deal inside me. I understood that our universe is contained in the mind. We may choose not to access to it, we may even deny its existence, but it is indeed there inside us. Shulgins professional activities continued to lean in the direction of psychopharmacology, but during this period he was unable to do much independent research. His opportunity for further research came in 1961 after his development of Zectran, the first biodegradable pesticide, in his book PIHKAL, Shulgin limits his pesticide days at Dow Chemical to one sentence in 978 pages. Dow Chemical Company, in return for Zectrans valuable patent, gave Shulgin great freedom, during this time, he created and patented drugs when Dow asked, and published findings on other drugs in journals such as Nature and the Journal of Organic Chemistry. Eventually, Dow Chemical requested that he no longer use their name on his publications, in late 1966, Shulgin left Dow in order to pursue his own interests. He first spent two years studying neurology at the University of California, San Francisco School of Medicine, leaving to work on a consulting project and he set up a home-based lab on his property, known as the Farm, and became a private consultant
15.
PiHKAL
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PiHKAL, A Chemical Love Story is a book by Dr. Alexander Shulgin and Ann Shulgin which was published in 1991. The subject of the work is psychoactive phenethylamine chemical derivatives, notably those that act as psychedelics and/or empathogen-entactogens, the main title is an acronym that stands for Phenethylamines I Have Known And Loved. The second part was made available by Shulgin on Erowid while the first part is available only in the printed text. While the reactions described are beyond the ability of people with a basic chemistry education, notable among these are the use of mercury-aluminum amalgam as a reducing agent and detailed suggestions on legal plant sources of important drug precursors such as safrole. The MDMA synthesis published in PIHKAL remains one of the most common methods of its manufacture to this day. Many countries have banned the major substances for which this book gives directions for synthesis, such as 2C-B, 2C-T-2, in the United Kingdom, all but phenethylamine are illegal. In 1994, two years after PIHKAL was published, the Drug Enforcement Administration raided Shulgins lab and requested that he turn over his DEA license. Richard Meyer, spokesman for DEAs San Francisco Field Division, has stated in reference to PIHKAL It is our opinion that those books are pretty much cookbooks on how to make illegal drugs. The Essential Amphetamines are what Shulgin describes as ten amphetamines that differ from natural products such as safrole or myristicin by an amine group. The list consists of, PMA2, 4-DMA3, 4-DMA MDA MMDA MMDA-3a MMDA-2 TMA TMA-2 DMMDA DMMDA-2 TeMA Not all of these chemicals are bioassayed in PIHKAL, some are merely mentioned. The so-called magical half-dozen refers to Shulgins self-rated most important phenethylamine compounds, 2C-B 2C-E 2C-T-2 2C-T-7 All six are now Schedule I controlled substances in the United States
16.
Concord, California
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Concord is the largest city in Contra Costa County, California. At the 2010 census, the city had a population of 122,067 making it the 8th largest city in the San Francisco Bay Area, founded in 1869 as the community of Todos Santos by Salvio Pacheco, the name was changed to Concord within months. The city is a major regional suburban East Bay center within the San Francisco Bay Area, Concord is located at 37°58′41″N 122°01′52″W. It is 29 miles northeast of San Francisco,22 miles northeast from Oakland,65 miles southwest of Sacramento, according to the United States Census Bureau, the city has a total area of 30.5 square miles, all of it land. Despite this, some crime and homelessness remain issues in the downtown area, to the north and east of downtown is the older residential area of Concord, with many homes dating back to before World War II. In the far edge of town is a primarily industrial area. The southeastern area of the city, centered along Clayton Road, is residential and was mostly developed in the 1960s and 1970s. In the southwest area of the city is the primarily Latino neighborhood known as Four Corners, centered around the intersection of Monument Boulevard, though it shares no border with Concord, Martinez is located almost immediately adjacent to Concord on the northwest. The North Concord BART station is known as Martinez BART. Concord has a hot summer Mediterranean climate, official data from the National Weather Service cooperative station in Concord shows average January temperatures are a maximum of 57.2 degrees Fahrenheit and a minimum of 41.6 °F. Average July temperatures are a maximum of 87.8 °F, there are an average of 45.0 days with highs of 90 °F or higher and 3.8 days with lows of 32 °F or lower. The highest recorded temperature was 110 °F on July 23,2006, the lowest record temperature was 24 °F on December 23,1998. Average annual precipitation is 18.31 inches, falling on an average of 57 days annually, the wettest year was 1995 with 26.62 inches and driest year was 2007 with 10.57 inches. The most rainfall in one month was 11.79 inches in December 2005, the valleys north of Mount Diablo were inhabited by the Miwok people, who hunted elk and fished in the numerous streams flowing from the mountain into the San Francisco Bay. In 1772, Spanish explorers began to cross the area, in 1834 the Mexican land grant Rancho Monte del Diablo at the base of Mount Diablo was granted to Salvio Pacheco. Concord was founded under the name of Todos Santos, on the initiative of Pacheco in 1869 and it achieved prominence in the 19th century as a result of most residents of Pacheco relocating to Concord to avoid the devastation of fire and flood which crippled Pachecos formerly booming economy. Concord was incorporated on February 5,1905, the area around Concord in the surrounding Ygnacio and Clayton Valleys was a large agricultural area. Crops that were grown included grapes, walnuts, wheat, hay, the area to the east was the site of a few enormous wheat ranches over 5,000 acres, and was almost a sea of wheat all the way to the marshes bordering Suisun Bay
17.
MDMA
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3, 4-Methylenedioxymethamphetamine, commonly known as ecstasy, is a psychoactive drug used primarily as a recreational drug. Desired effects include increased empathy, euphoria, and heightened sensations, when taken by mouth, effects begin after 30–45 minutes and last 3–6 hours. It is also sometimes snorted or smoked, as of 2017, MDMA has no accepted medical uses. Adverse effects of MDMA use include addiction, memory problems, paranoia, difficulty sleeping, teeth grinding, blurred vision, sweating, use may also lead to depression and fatigue. Deaths have been reported due to increased temperature and dehydration. MDMA increases the release and slows the reuptake of the serotonin, dopamine. It has stimulant and psychedelic effects, the initial increase is followed by a short-term decrease in the neurotransmitters. MDMA belongs to the substituted methylenedioxyphenethylamine and substituted amphetamine classes of drugs, MDMA was first made in 1912. It was used to improve psychotherapy beginning in the 1970s and became popular as a drug in the 1980s. MDMA is commonly associated with parties, raves, and electronic dance music. It is often mixed with other substances such as ephedrine, amphetamine. In 2014, between 9 and 29 million people between the ages of 15 and 64 used ecstasy and this was broadly similar to the percentage of people who use cocaine, amphetamines, and opioids, but fewer than for cannabis. In the United States, about 0.9 million people used ecstasy in 2010, MDMA is generally illegal in most countries. Limited exceptions are made for research. Researchers are investigating whether a few low doses of MDMA may assist in treating severe, in November 2016, phase 3 clinical trials for PTSD were approved by the United States Food and Drug Administration to assess effectiveness and safety. As of 2017, MDMA has no accepted medical indications, before it was widely banned, it saw limited use in therapy. A small number of therapists continue to use MDMA in therapy despite its illegal status, MDMA is often considered the drug of choice within the rave culture and is also used at clubs, festivals and house parties. In the rave environment, the effects from the music
18.
Vasoconstriction
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Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vessels, the process is particularly important in staunching hemorrhage and acute blood loss. When blood vessels constrict, the flow of blood is restricted or decreased and this makes the skin turn paler because less blood reaches the surface, reducing the radiation of heat. On a larger level, vasoconstriction is one mechanism by which the body regulates, medications causing vasoconstriction, also known as vasoconstrictors, are one type of medicine used to raise blood pressure. Generalized vasoconstriction usually results in an increase in blood pressure. The extent of vasoconstriction may be slight or severe depending on the substance or circumstance, many vasoconstrictors also cause pupil dilation. Medications that cause vasoconstriction include, antihistamines, decongestants, and stimulants, severe vasoconstriction may result in symptoms of intermittent claudication. The mechanism that leads to results from the increased concentration of calcium within vascular smooth muscle cells. However, the mechanisms for generating an increased intracellular concentration of calcium depends on the vasoconstrictor. Smooth muscle cells are capable of generating action potentials, but this mechanism is utilized for contraction in the vasculature. Hormonal or pharmokinetic components are more physiologically relevant, two common stimuli for eliciting smooth muscle contraction are circulating epinephrine and activation of the sympathetic nervous system that directly innervates the muscle. These compounds interact with cell surface adrenergic receptors, the rise in intracellular calcium complexes with calmodulin, which in turn activates myosin light-chain kinase. This enzyme is responsible for phosphorylating the light chain of myosin to stimulate cross-bridge cycling and this reduction in calcium removes the stimulus necessary for contraction, allowing for a return to baseline. Factors that trigger vasoconstriction can be of exogenous or endogenous origin, ambient temperature is an example of the former. Cutaneous vasoconstriction will occur because of the exposure to the severe cold. Examples of endogenous factors include the nervous system, circulating hormones. Examples include amphetamines, antihistamines and cocaine, many are used in medicine to treat hypotension and as topical decongestants. Vasoconstrictors are also used clinically to increase blood pressure or to reduce blood flow
19.
2,5-Dimethoxy-4-iodoamphetamine
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2, 5-Dimethoxy-4-iodoamphetamine is a psychedelic drug and a substituted amphetamine. Unlike other substituted amphetamines, however, it is not a stimulant, DOI has a stereocenter and R--DOI is the more active stereoisomer. In neuroscience research, -R--DOI is used as a radioligand and indicator of the presence of 5-HT2A serotonin receptors, dOIs effects have been compared to LSD, although there are differences that experienced users can distinguish. Besides the longer duration, the trip tends to be more energetic than an LSD trip, with more body load, the after effects include residual stimulation and difficulty sleeping, which, depending on the dose, may persist for days. It is sometimes sold as a substitute for LSD, or even sold falsely as LSD, research suggests that administration of -DOI blocks pulmonary inflammation, mucus hyper-production, airway hyper-responsiveness and turns off key genes in in-lung immune response. These effects block the development of asthma in a mouse model. DOI is a 5-HT2A, 5-HT2B and 5-HT2C receptor agonist, DOI has been shown to be an extremely potent inhibitor of tumour necrosis factor-alpha inflammation at picomolar concentrations in cell studies. This could make DOI and other 5-HT2A agonists an entirely new area for development of treatments for these conditions. DOI has also shown to induce rapid growth and reorganization of dendritic spines and synaptic connections with other neurons. DOI was first synthesized by Alexander Shulgin, the radioactive iodine-125 form of DOI for PET imaging was first developed in the lab of David E. Nichols. This would appear to be the first indication that DOI has found widespread use as a recreational drug in the UK. An extremely large increase in DOI sales has been seen in Adelaide and it is commonly sold as LSD or just trips. The Standard for the Uniform Scheduling of Medicines and Poisons of Australia does not list DOI as a prohibited substance, listed as a Schedule 1 as it is an analogue of amphetamine. The CDSA was updated as a result of the Safe Streets Act changing amphetamines from Schedule 3 to Schedule 1. DOI is not scheduled in the United States, but it is likely that DOI would be considered an analog, in which case, DOI is occasionally used in animal and in vitro research. Scheduling DOI could cause problems for medical researchers, DOI is a Schedule I controlled substance in the state of Florida. 2, 5-Dimethoxy-4-Substituted Amphetamines DOF DOB DOC Erowid about DOI The Lycaeum about DOI PiHKAL entry DOI Entry in PiHKAL • info
20.
2C-B
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2C-B or 2, 5-dimethoxy-4-bromophenethylamine is a psychedelic drug of the 2C family. It was first synthesized by Alexander Shulgin in 1974, in Shulgins book PiHKAL, the dosage range is listed as 12–24 mg. 2C-B is sold as a white powder sometimes pressed in tablets or gel caps and is also referred to by a number of other names. The drug is taken orally, but can also be insufflated or vaporized. 2C-B was synthesized from 2, 5-dimethoxybenzaldehyde by Alexander Shulgin in 1974 and it first saw use among the psychiatric community as an aid during therapy. It was considered one of the best drugs for this purpose because of its duration, relative absence of side effects. Shortly after becoming popular in the community, it became popular recreationally. 2C-B was first sold commercially as an aphrodisiac under the trade name Erox, for several years, it was available as tablets in Dutch smart shops under the name Nexus. Internationally, 2C-B is a Schedule II drug under the Convention on Psychotropic Substances, in the Netherlands, 2C-B became a list I substance of the Opium Law despite no health incidents occurring. Following the ban, other phenethylamines were sold in place of 2C-B until the Netherlands became the first country in the world to ban 2C-I, 2C-T-2 and this became permanent law on July 2,1995. 2C-B first became popularized in the United States as a legal substitute for the street drug Ecstasy when MDMA became illegal in 1985. Many 2C-B users are young adults who attend raves, though 2C-B is still used in the rave subculture, commonly mistaken for and/or sold as Ecstasy, its intentional use has become more common. In recent years, 2C-B has emerged as the drug of choice for club drug users in Colombia, street prices range between $10 and $30 per tablet in the United States when bought in small quantities. Larger retail purchases cost between $200 and $500 per gram, wholesale purchases of 2C-B can lower the price to a range of $100 to $300 per gram. The September 1998 Journal of Analytical Toxicology reported that very little data exists about the properties, metabolism. The relationship between its use and death are unknown, the common oral recreational dose is around 15–25 mg, at which visual and auditory effects are experienced. Severe adverse reactions are rare, but use of 2C-B has been linked to significant injury in one case where the dosage is unknown. It was reported in PiHKAL, by Alexander Shulgin, that a psychologist had accidentally taken a 100 mg dose orally without apparent harm, street purity of 2C-B, when tested, has been found to be relatively high. Researchers in Spain found that 2C-B samples in the country doubled between 2006 and 2009, switched from primarily powder form to tablets, and exhibited low falsification rates, the authors suggested that this compound was a by-product of 2C-B synthesis
21.
5-HT2A receptor
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The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor. This is the main excitatory receptor subtype among the GPCRs for serotonin, although 5-HT2A may also have an effect on certain areas such as the visual cortex. This receptor was first noted for its importance as a target of serotonergic psychedelic drugs such as LSD, later it came back to prominence because it was also found to be mediating, at least partly, the action of many antipsychotic drugs, especially the atypical ones. 5-HT2A may be a receptor for the spread of the human polyoma virus called JC virus. Downregulation of post-synaptic 5-HT2A receptor is an adaptive process provoked by chronic administration of selective serotonin reuptake inhibitors, deceased suicidal and otherwise depressed patients have had more 5-HT2A receptors than normal patients. These findings suggest that post-synaptic 5-HT2A overdensity is involved in the pathogenesis of depression, 5-HT2A is thought to correspond to what was originally described as D subtype of 5-HT receptors by Gaddum and Picarelli. Later it was shown that the 5-HT2 was very close to 5-HT1C and thus were clubbed together, thus the 5-HT2 receptor family is composed of three separate molecular entities, the 5-HT2A, the 5-HT2B and the 5-HT2C receptors. 5-HT2A is expressed throughout the central nervous system. It is expressed near most of the serotoninergic terminal rich areas, including neocortex, in the rat cerebellum, the protein has also been found in the Golgi cells of the granular layer, and in the Purkinje cells. In the periphery, it is expressed in platelets and many cell types of the cardiovascular system, in fibroblasts. Additionally, 5-HT2A mRNA expression has been observed in human monocytes, the 5-HT2A receptor is known primarily to couple to the Gαq signal transduction pathway. Upon receptor stimulation with agonist, Gαq and β-γ subunits dissociate to initiate downstream effector pathways, Gαq stimulates phospholipase C activity, which subsequently promotes the release of diacylglycerol and inositol triphosphate, which in turn stimulate protein kinase C activity and Ca2+ release. Other 5-HT2A agonists like LSD also have potent anti-inflammatory effects against TNF-alpha-induced inflammation, activation of the 5-HT2A receptor in hypothalamus causes increases in hormonal levels of oxytocin, prolactin, ACTH, corticosterone, and renin. A very large family of derivatives from these three classes has been developed, and their structure-activity relationships have been extensively researched, agonists acting at 5-HT2A receptors located on the apical dendrites of pyramidal cells within regions of the prefrontal cortex are believed to mediate hallucinogenic activity. Newer findings reveal that psychoactive effects of classic psychedelics are mediated by the receptor heterodimer 5-HT2A–mGlu2, agonists enhance dopamine in PFC, enhances memory and plays an active role in attention and learning. O-4310, 5-HT2A selective, claimed to have 100x selectivity over 5-HT2C and be inactive at 5-HT2B PHA-57378, dual 5-HT2A / 5-HT2C agonist, anxiolytic effects in animal studies. 25C-NBOMe Methysergide, a congener of methylergonovine, used in treatment of migraine blocks 5-HT2A and 5-HT2C receptors, oSU-6162 acts as a partial agonist at both 5-HT2A and dopamine D2 receptors 25CN-NBOH, 100x selectivity for 5-HT2A over 5-HT2C, 46x selectivity over 5-HT2B. Efavirenz, a drug, produces psychiatric side effects thought to be mediated by 5-HT2A
22.
5-HT2B receptor
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5-Hydroxytryptamine receptor 2B also known as serotonin receptor 2B is a protein that in humans is encoded by the HTR2B gene. 5-HT2B is a member of the 5-HT2 receptor family that binds the neurotransmitter serotonin, the 5-HT2 receptors mediate many of the central and peripheral physiologic functions of serotonin. The 5-HT2B receptor stimulation can also lead to proliferation of cardiac valves fibroblasts. 5-HT2B receptors have also strongly implicated in drug-induced valvular heart disease. In this context, it is considered to be an antitarget. The structure of the 5-HT2B receptor was recently solved in complex with the valvulopathogenic drug ergotamine, as of 2009, few highly selective 5-HT2B receptor ligands have been discovered, although numerous potent non-selective compounds are known, particularly agents with concomitant 5-HT2C binding. Selective BW-723C86, fair functional subtype selectivity, almost full agonist, MDMA MDA MEM Pergolide Cabergoline Norfenfluramine Chlorphentermine Aminorex mCPP Bromo-dragonfly DMT 5-MeO-DMT LSD-25 - About equal affinity for human cloned 5-HT2B and 5-HT2A receptors. Psilocin Agomelatine - primarily a melatonin Mt1/Mt2 receptor agonist, with a less potent antagonism of 5-HT2B, more recent research has focused on possible application of 5-HT2B antagonists as treatments for chronic heart disease. Research claims serotonin 5-HT2B receptors have effect on liver regeneration, IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology, human HTR2B genome location and HTR2B gene details page in the UCSC Genome Browser. This article incorporates text from the United States National Library of Medicine, which is in the public domain
23.
5-HT2C receptor
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The 5-HT2C receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin. It is a G protein-coupled receptor that is coupled to Gq/G11, HTR2C denotes the human gene encoding for the receptor, that in humans is located at the X chromosome. As males have one copy of the gene and in one of the two copies of the gene is repressed, polymorphisms at this receptor can affect the two sexes to differing extent. At the cell surface the receptor exists as a homodimer, 5-HT2C receptors are widely distributed across the periphery and brain in humans. The 5-HT2C receptor is one of the binding sites for serotonin. Activation of this receptor by serotonin inhibits dopamine and norepinephrine release in areas of the brain. 5-HT2C receptors are claimed to significantly regulate mood, anxiety, feeding, 5-HT2C receptors regulate dopamine release in the striatum, prefrontal cortex, nucleus accumbens, hippocampus, hypothalamus, and amygdala, among others. Research indicates that some victims have an abnormally high number of 5-HT2C receptors in the prefrontal cortex. There is some mixed evidence that agomelatine, a 5-HT2C antagonist, is an effective antidepressant, antagonism of 5-HT2C receptors by agomelatine results in an increase of dopamine and norepinephrine activity in the frontal cortex. Many atypical antipsychotics block 5-HT2C receptors, but their use is limited by multiple undesirable actions on various neurotransmitters and receptors. Fluoxetine acts as a direct 5-HT2C antagonist in addition to inhibiting serotonin reuptake, however, an overactivity of 5-HT2C receptors may contribute to depressive and anxiety symptoms in a certain population of patients. Activation of 5-HT2C by serotonin is responsible for many of the side effects of SSRI and SNRI medications, such as sertraline, paroxetine, venlafaxine. Some of the anxiety caused by SSRIs is due to excessive signalling at 5-HT2C. Over a period of 1–2 weeks, the receptor begins to downregulate, along with the downregulation of 5-HT2A, 5-HT1A and this downregulation parallels the onset of the clinical benefits of SSRIs. 5-HT2C receptors exhibit constitutive activity in vivo, and may retain the ability to influence neurotransmission in the absence of ligand occupancy, thus, 5-HT2C receptors do not require binding by a ligand in order to exhibit influence on neurotransmission. Inverse agonists may be required to fully extinguish 5-HT2C constitutive activity, 5-HT2C receptors mediate the release and increase of extracellular dopamine in response to many drugs, including caffeine, nicotine, amphetamine, morphine, cocaine, and others. 5-HT2C antagonism increases dopamine release in response to reinforcing drugs, feeding, social interaction, and sexual activity all release dopamine subject to inhibition of 5-HT2C. Increased 5-HT2C expression reduces dopamine release in both the presence and absence of stimuli, conditions that increase cytokine levels in the human body may have potential to raise 5-HT2C gene expression in the brain
24.
Agonist
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An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response. Whereas an agonist causes an action, an antagonist blocks the action of the agonist, receptors can be activated by either endogenous or exogenous agonists, resulting in a biological response. A physiological agonist is a substance that creates the same bodily responses but does not bind to the same receptor, an endogenous agonist for a particular receptor is a compound naturally produced by the body that binds to and activates that receptor. For example, the endogenous agonist for serotonin receptors is serotonin, a superagonist is a compound that is capable of producing a greater maximal response than the endogenous agonist for the target receptor, and thus has an efficacy of more than 100%. Full agonists bind and activate a receptor, producing full efficacy at that receptor, one example of a drug that acts as a full agonist is isoproterenol, which mimics the action of adrenaline at β adrenoreceptors. Another example is morphine, which mimics the actions of endorphins at μ-opioid receptors throughout the nervous system. Partial agonists also bind and activate a receptor, but have only partial efficacy at the receptor relative to a full agonist. Agents like buprenorphine are used to treat opiate dependence for this reason, as they produce milder effects on the receptor with lower dependence. An inverse agonist is an agent that binds to the same receptor binding-site as an agonist for that receptor, inverse agonists exert the opposite pharmacological effect of a receptor agonist, not merely an absence of the agonist effect as seen with antagonist. An example is the inverse agonist rimonabant. A co-agonist works with other co-agonists to produce the desired effect together, NMDA receptor activation requires the binding of both glutamate, glycine and D-serine co-agonists. An irreversible agonist is a type of agonist that binds permanently to a receptor through the formation of covalent bonds, a few of these have been described. A selective agonist is selective for a type of receptor. E. g. buspirone is a selective agonist for serotonin 5-HT1A, terms that describe this phenomenon are functional selectivity, protean agonism, or selective receptor modulators. Potency is the amount of agonist needed to elicit a desired response, the potency of an agonist is inversely related to its EC50 value. The EC50 can be measured for a given agonist by determining the concentration of agonist needed to elicit half of the biological response of the agonist. The EC50 value is useful for comparing the potency of drugs with similar efficacies producing physiologically similar effects, the smaller the EC50 value, the greater the potency of the agonist, the lower the concentration of drug that is required to elicit the maximum biological response. This relationship, termed the index, is defined as the ratio TD50, ED50
25.
TAAR1
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Trace amine-associated receptor 1 is a protein that in humans is encoded by the TAAR1 gene. TAAR1 was discovered in 2001 by two independent groups of investigators, Borowski et al. and Bunzow et al, TAAR1 is one of six functional trace amine-associated receptors in humans, which are so named for their ability to bind endogenous amines that occur in tissues at trace concentrations. TAAR1 is a high-affinity receptor for amphetamine, methamphetamine, dopamine, the primary endogenous ligands of the human TAAR1 receptor, by rank order of potency, are, tyramine > β-phenethylamine > dopamine = octopamine. TAAR1 was discovered independently by Borowski et al. and Bunzow et al. in 2001, the resulting sequence was not found in any database and coded for TAAR1. TAAR1 shares structural similarities with the class A rhodopsin GPCR subfamily and it has 7 transmembrane domains with short N and C terminal extensions. TAAR1 shares a predictive peptide motif with all other TAARs and this motif overlaps with transmembrane domain VII, and its identity is NSXXNPXXXXXXWF. TAAR1 and its homologues have ligand pocket vectors that utilize a sets of 35 amino acids known to be involved directly in receptor-ligand interaction. All TAAR genes are located on a single chromosome spanning 109kb of human chromosome 6q23.1,192 kb of mouse chromosome 10A4, each TAAR is derived from a single exon, except for TAAR2, which is coded by two exons. To date, TAAR1 has been identified and cloned in five different mammal genomes, human, mouse, rat, monkey, and chimpanzee. In rats, mRNA for TAAR1 is found at low to moderate levels in peripheral tissues like the stomach, kidney, and lungs, rhesus monkey Taar1 and human TAAR1 share high sequence similarity, and TAAR1 mRNA is highly expressed in the same important monoaminergic regions of both species. These regions include the dorsal and ventral caudate nucleus, putamen, substantia nigra, nucleus accumbens, ventral area, locus coeruleus, amygdala. TAAR1 has also identified in human astrocytes. TAAR1 is the only TAAR subtype not found in the olfactory epithelium, human TAAR1 is an intracellular receptor expressed within the presynaptic terminal of monoamine neurons. In model cell systems, hTAAR1 has extremely poor membrane expression, a method to induce hTAAR1 membrane expression has been used to study its pharmacology via a bioluminescence resonance energy transfer cAMP assay. TAAR1 forms GPCR oligomers with monoamine autoreceptors in neurons in vivo, some of the human trace amines include tryptamine, phenethylamine, N-methylphenethylamine, p-tyramine, m-tyramine, N-methyltyramine, p-octopamine, m-octopamine, and synephrine. These share structural similarities with the three monoamines, serotonin, dopamine, and norepinephrine. Each ligand has a different potency, measured as increases cyclic AMP concentration after the binding event, the rank order of potency for the primary endogenous ligands at hTAAR1 is, tyramine > β-phenethylamine > dopamine = octopamine. Thyronamines are molecular derivatives of the hormone and are very important for endocrine system function
26.
Convention on Psychotropic Substances
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The Single Convention on Narcotic Drugs of 1961 could not ban the many newly discovered psychotropics, since its scope was limited to drugs with cannabis, coca, and opium-like effects. The Convention, which contains import and export restrictions and other rules aimed at limiting drug use to scientific and medical purposes, as of 2013,183 member states are Parties to the treaty. Many laws have passed to implement the Convention, including the U. S. Psychotropic Substances Act, the UK Misuse of Drugs Act 1971. Adolf Lande, under the direction of the United Nations Office of Legal Affairs, the Commentary, published in 1976, is an invaluable aid to interpreting the treaty and constitutes a key part of its legislative history. This treaty, signed in 1988, regulates precursor chemicals to drugs controlled by the Single Convention and it also strengthens provisions against money laundering and other drug-related crimes. International drug control began with the 1912 International Opium Convention, a treaty which adopted import and export restrictions on the opium poppys psychoactive derivatives, after the United Nations was formed in 1945, those enforcement functions passed to the UN. During the 1960s, drug use increased in Western developed nations, young people began using hallucinogenic, stimulant, and other drugs on a widespread scale that has continued to the present. In many jurisdictions, police had no laws under which to prosecute users and traffickers of these new drugs, LSD, the language of the Single Convention and its legislative history precluded any interpretation that would allow international regulation of these drugs under that treaty. A new convention, with a scope, would be required in order to bring those substances under control. Using the Single Convention as a template, the Commission prepared a draft convention which was forwarded to all UN member states, the Secretary-General of the United Nations scheduled a conference for early 1971 to finalize the treaty. Meanwhile, countries had already begun passing legislation to implement the draft treaty, in 1969, Canada added Part IV to its Food and Drugs Act, placing a set of restricted substances, including LSD, DMT, and MDA, under federal control. In 1970, the United States completely revamped its existing drug laws by enacting the Controlled Substances Act. In 1971, the United Kingdom passed the Misuse of Drugs Act 1971, a host of other nations followed suit. The conference convened on 11 January 1971, Nations split into two rival factions, based on their interests. According to a Senate of Canada report, One group included mostly developed nations with powerful pharmaceutical industries, the other group consisted of developing states. with few psychotropic manufacturing facilities. The organic drugmaking states that had suffered economically from the Single Conventions restrictions on cannabis, coca, the synthetic drug-producing states opposed those restrictions. The Conventions adoption marked a milestone in the development of the global drug control regime. As of June 2013, there are 183 state parties to the convention and this total includes 182 member states of the United Nations and the Holy See
27.
International Standard Book Number
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The International Standard Book Number is a unique numeric commercial book identifier. An ISBN is assigned to each edition and variation of a book, for example, an e-book, a paperback and a hardcover edition of the same book would each have a different ISBN. The ISBN is 13 digits long if assigned on or after 1 January 2007, the method of assigning an ISBN is nation-based and varies from country to country, often depending on how large the publishing industry is within a country. The initial ISBN configuration of recognition was generated in 1967 based upon the 9-digit Standard Book Numbering created in 1966, the 10-digit ISBN format was developed by the International Organization for Standardization and was published in 1970 as international standard ISO2108. Occasionally, a book may appear without a printed ISBN if it is printed privately or the author does not follow the usual ISBN procedure, however, this can be rectified later. Another identifier, the International Standard Serial Number, identifies periodical publications such as magazines, the ISBN configuration of recognition was generated in 1967 in the United Kingdom by David Whitaker and in 1968 in the US by Emery Koltay. The 10-digit ISBN format was developed by the International Organization for Standardization and was published in 1970 as international standard ISO2108, the United Kingdom continued to use the 9-digit SBN code until 1974. The ISO on-line facility only refers back to 1978, an SBN may be converted to an ISBN by prefixing the digit 0. For example, the edition of Mr. J. G. Reeder Returns, published by Hodder in 1965, has SBN340013818 -340 indicating the publisher,01381 their serial number. This can be converted to ISBN 0-340-01381-8, the check digit does not need to be re-calculated, since 1 January 2007, ISBNs have contained 13 digits, a format that is compatible with Bookland European Article Number EAN-13s. An ISBN is assigned to each edition and variation of a book, for example, an ebook, a paperback, and a hardcover edition of the same book would each have a different ISBN. The ISBN is 13 digits long if assigned on or after 1 January 2007, a 13-digit ISBN can be separated into its parts, and when this is done it is customary to separate the parts with hyphens or spaces. Separating the parts of a 10-digit ISBN is also done with either hyphens or spaces, figuring out how to correctly separate a given ISBN number is complicated, because most of the parts do not use a fixed number of digits. ISBN issuance is country-specific, in that ISBNs are issued by the ISBN registration agency that is responsible for country or territory regardless of the publication language. Some ISBN registration agencies are based in national libraries or within ministries of culture, in other cases, the ISBN registration service is provided by organisations such as bibliographic data providers that are not government funded. In Canada, ISBNs are issued at no cost with the purpose of encouraging Canadian culture. In the United Kingdom, United States, and some countries, where the service is provided by non-government-funded organisations. Australia, ISBNs are issued by the library services agency Thorpe-Bowker
28.
International Standard Serial Number
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An International Standard Serial Number is an eight-digit serial number used to uniquely identify a serial publication. The ISSN is especially helpful in distinguishing between serials with the same title, ISSN are used in ordering, cataloging, interlibrary loans, and other practices in connection with serial literature. The ISSN system was first drafted as an International Organization for Standardization international standard in 1971, ISO subcommittee TC 46/SC9 is responsible for maintaining the standard. When a serial with the content is published in more than one media type. For example, many serials are published both in print and electronic media, the ISSN system refers to these types as print ISSN and electronic ISSN, respectively. The format of the ISSN is an eight digit code, divided by a hyphen into two four-digit numbers, as an integer number, it can be represented by the first seven digits. The last code digit, which may be 0-9 or an X, is a check digit. Formally, the form of the ISSN code can be expressed as follows, NNNN-NNNC where N is in the set, a digit character. The ISSN of the journal Hearing Research, for example, is 0378-5955, where the final 5 is the check digit, for calculations, an upper case X in the check digit position indicates a check digit of 10. To confirm the check digit, calculate the sum of all eight digits of the ISSN multiplied by its position in the number, the modulus 11 of the sum must be 0. There is an online ISSN checker that can validate an ISSN, ISSN codes are assigned by a network of ISSN National Centres, usually located at national libraries and coordinated by the ISSN International Centre based in Paris. The International Centre is an organization created in 1974 through an agreement between UNESCO and the French government. The International Centre maintains a database of all ISSNs assigned worldwide, at the end of 2016, the ISSN Register contained records for 1,943,572 items. ISSN and ISBN codes are similar in concept, where ISBNs are assigned to individual books, an ISBN might be assigned for particular issues of a serial, in addition to the ISSN code for the serial as a whole. An ISSN, unlike the ISBN code, is an identifier associated with a serial title. For this reason a new ISSN is assigned to a serial each time it undergoes a major title change, separate ISSNs are needed for serials in different media. Thus, the print and electronic versions of a serial need separate ISSNs. Also, a CD-ROM version and a web version of a serial require different ISSNs since two different media are involved, however, the same ISSN can be used for different file formats of the same online serial
29.
PubMed Identifier
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PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine at the National Institutes of Health maintains the database as part of the Entrez system of information retrieval, from 1971 to 1997, MEDLINE online access to the MEDLARS Online computerized database primarily had been through institutional facilities, such as university libraries. PubMed, first released in January 1996, ushered in the era of private, free, home-, the PubMed system was offered free to the public in June 1997, when MEDLINE searches via the Web were demonstrated, in a ceremony, by Vice President Al Gore. Information about the journals indexed in MEDLINE, and available through PubMed, is found in the NLM Catalog. As of 5 January 2017, PubMed has more than 26.8 million records going back to 1966, selectively to the year 1865, and very selectively to 1809, about 500,000 new records are added each year. As of the date,13.1 million of PubMeds records are listed with their abstracts. In 2016, NLM changed the system so that publishers will be able to directly correct typos. Simple searches on PubMed can be carried out by entering key aspects of a subject into PubMeds search window, when a journal article is indexed, numerous article parameters are extracted and stored as structured information. Such parameters are, Article Type, Secondary identifiers, Language, publication type parameter enables many special features. As these clinical girish can generate small sets of robust studies with considerable precision, since July 2005, the MEDLINE article indexing process extracts important identifiers from the article abstract and puts those in a field called Secondary Identifier. The secondary identifier field is to store numbers to various databases of molecular sequence data, gene expression or chemical compounds. For clinical trials, PubMed extracts trial IDs for the two largest trial registries, ClinicalTrials. gov and the International Standard Randomized Controlled Trial Number Register, a reference which is judged particularly relevant can be marked and related articles can be identified. If relevant, several studies can be selected and related articles to all of them can be generated using the Find related data option, the related articles are then listed in order of relatedness. To create these lists of related articles, PubMed compares words from the title and abstract of each citation, as well as the MeSH headings assigned, using a powerful word-weighted algorithm. The related articles function has been judged to be so precise that some researchers suggest it can be used instead of a full search, a strong feature of PubMed is its ability to automatically link to MeSH terms and subheadings. Examples would be, bad breath links to halitosis, heart attack to myocardial infarction, where appropriate, these MeSH terms are automatically expanded, that is, include more specific terms. Terms like nursing are automatically linked to Nursing or Nursing and this important feature makes PubMed searches automatically more sensitive and avoids false-negative hits by compensating for the diversity of medical terminology. The My NCBI area can be accessed from any computer with web-access, an earlier version of My NCBI was called PubMed Cubby
30.
Hallucinogen
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A hallucinogen is a psychoactive agent which can cause hallucinations, perceptual anomalies, and other substantial subjective changes in thoughts, emotion, and consciousness. The common types of hallucinogens are psychedelics, dissociatives and deliriants, although hallucinations are a common symptom of amphetamine psychosis, amphetamines are not considered hallucinogens, as they are not a primary effect of the drugs themselves. While hallucinations can occur when abusing stimulants, the nature of stimulant psychosis is not unlike delirium, a debate persists on criteria which would easily differentiate a substance which is psychedelic from one hallucinogenic. Sir Thomas Browne in 1646 coined the term hallucination from the Latin word alucinari meaning to wander in the mind, the term psychedelic is derived from the Ancient Greek words psychē and dēloun, or mind-revealing. A hallucinogen and a psychedelic may refer correctly to the same substance, hallucinations and psychedelia may both refer to the same aspects of subjective experience in a given instance. A hallucinogen in this sense refers to any substance which causes changes in perception or hallucinations. In contrast to Hollisters original criteria, adverse effects may predominate with some hallucinogens with this application of the term, the word psychedelic was coined to express the idea of a drug that makes manifest a hidden but real aspect of the mind. One explanatory model for the experiences provoked by psychedelics is the reducing valve concept, in this view, the drugs disable the brains filtering ability to selectively prevent certain perceptions, emotions, memories and thoughts from ever reaching the conscious mind. This effect has been described as mind expanding, or consciousness expanding, many designer drugs and research chemicals are hallucinogenic in nature, such as those in the 2C and NBOMe families. Dissociatives produce analgesia, amnesia and catalepsy at anesthetic doses, dissociative symptoms include the disruption or compartmentalization of. the usually integrated functions of consciousness, memory, identity or perception. p. 523 Dissociation of sensory input can cause derealization, the perception of the world as being dream-like or unreal. The primary dissociatives achieve their effect through blocking the signals received by the NMDA receptor set and include ketamine, methoxetamine, phencyclidine, dextromethorphan, however, dissociation is also remarkably administered by salvinorin As potent κ-opioid receptor agonism. Some dissociatives can have CNS depressant effects, thereby carrying similar risks as opioids, DXM in higher doses can increase heart rate and blood pressure and still depress respiration. Inversely, PCP can have unpredictable effects and has often been classified as a stimulant. While many have reported that they feel no pain while under the effects of PCP, DXM and Ketamine, this does not fall under the usual classification of anesthetics in recreational doses. Rather, true to their name, they process pain as a kind of far away sensation, pain, although present, becomes a disembodied experience, as for probably the most common dissociative, nitrous oxide, the principal risk seems to be due to oxygen deprivation. Injury from falling is also a danger, as nitrous oxide may cause loss of consciousness. Because of the level of physical activity and relative imperviousness to pain induced by PCP
31.
2C-B-FLY
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2C-B-FLY is a psychedelic phenethylamine of the 2C family. It was first synthesized by Aaron P. Monte, the full name of the chemical is 2-ethanamine. It has been subject to formal study, but its appearance as a designer drug has led the DEA to release analytical results for 2C-B-FLY. In theory, dihydrodifuran analogues of any of the 2Cx / DOx family of drugs could be made, the larger saturated hexahydrobenzodipyran ring derivatives have been referred to as butterfly compounds. The 8-bromo group can also be replaced by groups to give compounds such as TFMFly. A large number of symmetrical and unsymmetrical derivatives can be produced by using different combinations of ring systems, because the 2- and 5- positions are not equivalent, all unsymmetrical combinations also have two possible positional isomers, with different potencies at the various 5-HT2 subtypes. A large number of possible combinations have been synthesised and tested for activity, alexander Shulgin lists a dosage of 2C-B-FLY at 10 mg orally. 2C-B-FLY produces psychedelic effects that last 6–8 hours, or up to 12 hours in larger doses, the toxicity of 2C-B-FLY in humans is unknown. As of October 31st,2016, 2C-B-FLY is a substance in Canada. Http, //gazette. gc. ca/rp-pr/p2/2016/2016-05-04/html/sor-dors72-eng. php 2C-B-FLY is unscheduled and uncontrolled in the United States, however, it may fall under the scope of the Federal Analog Act if it is intended for human consumption given its similarity to 2C-B. 2C-B-FLY Entry at Erowid 2C-B-FLY Entry at Isomerdesign
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. PMID 20126400.