1.
Regulation of therapeutic goods
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The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the level by a single agency. In other jurisdictions they are regulated at the level, or at both state and national levels by various bodies, as is the case in Australia. The role of therapeutic goods regulation is designed mainly to protect the health, regulation is aimed at ensuring the safety, quality, and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered before they are allowed to be marketed, there is usually some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers. Therapeutic goods in Australia are regulated by the Therapeutic Goods Administration, there are 5 main categories, Normal Medicines - Cough, cold and fever medicines, antiseptics, vitamins and others. Sold freely in pharmacies and some large supermarkets, red Stripe Medicines - These medicines are sold only with medical prescription. Antibiotics, Anti allergenics, Anti inflammatories, and other medicines, in Brazil, governmental control is loose on this type, it is not uncommon to buy this type of prescription medicine over the counter without a prescription. Red Stripe Psychoactive Medicines - These medicines are only with a Special Control white medical prescription with carbon copy. The original must be retained by the pharmacist after the sale, Drugs include anti-depressants, anti-convulsants, some sleep aids, anti-psychotics and other non-habit-inducing controlled medicines. Though some consider them habit inducing, anabolic steroids are also regulated under this category, black Stripe Medicines - These medicines are sold only with the Blue B Form medical prescription, which is valid for 30 days and must be retained by the pharmacist after the sale. Includes sedatives, some anorexic inducers and other habit-inducing controlled medicines, includes amphetamines and other stimulants, opioids and other strong habit-forming controlled medicines. In Canada, regulation of goods are governed by the Food and Drug Act. In addition, the Controlled Drugs and Substances Act requires additional regulatory requirements for controlled drugs, the regulation of drugs in Burma is governed by the Food and Drug Administration and Food and Drug Board of Authority. The regulation of drugs in China is governed by the China Food, Medicines for Human Use in the United Kingdom are regulated by the Medicines and Healthcare products Regulatory Agency. The availability of drugs is regulated by classification by the MHRA as part of marketing authorisation of a product, Medicines in the Republic of Ireland are regulated according to the Misuse of Drugs Regulations 1988. Controlled drugs are divided into five categories based on their potential for misuse, cD1, cannabis, lysergamide, coca leaf, etc. Use prohibited except in limited circumstances where a license has been granted, CD2, amphetamine, methadone, morphine, fentanyl, oxycodone, tapentadol, etc
2.
Controlled Substances Act
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The Controlled Substances Act is the statute establishing federal U. S. drug policy under which the manufacture, importation, possession, use and distribution of certain substances is regulated. It was passed by the 91st United States Congress as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970, the Act also served as the national implementing legislation for the Single Convention on Narcotic Drugs. The legislation created five Schedules, with varying qualifications for a substance to be included in each, classification decisions are required to be made on criteria including potential for abuse, currently accepted medical use in treatment in the United States, and international treaties. The nation first outlawed addictive drugs in the early 1900s and the International Opium Convention helped lead international agreements regulating trade, the Food and Drugs Act of 1906 was the beginning of over 200 laws concerning public health and consumer protections. Others were the Federal Food, Drug, and Cosmetic Act, in 1969, President Richard Nixon announced that the Attorney General, John N. Shafer—to study cannabis abuse in the United States. It implies an overwhelming indictment of the behavior which we believe is not appropriate, the actual and potential harm of use of the drug is not great enough to justify intrusion by the criminal law into private behavior, a step which our society takes only with the greatest reluctance. According to David T. Courtwright, the Act was part of a reform package designed to rationalize. It eliminated mandatory minimum sentences and provided support for drug treatment, king notes that the rehabilitation clauses were added as a compromise to Senator Jim Hughes, who favored a moderate approach. The bill, as introduced by Senator Everett Dirksen, ran to 91 pages, since its enactment in 1970, the Act has been amended several times, The Medical Device Amendments of 1976. The Psychotropic Substances Act of 1978 added provisions implementing the Convention on Psychotropic Substances, the Controlled Substances Penalties Amendments Act of 1984. The Ryan Haight Online Pharmacy Consumer Protection Act of 2008 The Electronic Prescriptions for Controlled Substances 2010, the Controlled Substances Act consists of 2 subchapters. Subchapter II describes the laws for exportation and importation of controlled substances, again specifying fines, the Drug Enforcement Administration was established in 1973, combining the Bureau of Narcotics and Dangerous Drugs and Customs drug agents. When a petition is received by the DEA, the agency begins its own investigation of the drug and this request is sent to the Assistant Secretary of Health of HHS. Under certain circumstances, the Government may temporarily schedule a drug without following the normal procedure, an example is when international treaties require control of a substance. In addition,21 U. S. C. §811 allows the Attorney General to temporarily place a substance in Schedule I to avoid an imminent hazard to the public safety, in any case, once these proceedings are complete, the temporary order is automatically vacated. Unlike ordinary scheduling proceedings, such orders are not subject to judicial review. The CSA also creates a system of distribution for those authorized to handle controlled substances. The cornerstone of this system is the registration of all those authorized by the DEA to handle controlled substances
3.
Pharmacokinetics
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Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as, pharmaceutical drugs, pesticides, food additives, cosmetic ingredients, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, both together influence dosing, benefit, and adverse effects, as seen in PK/PD models. Pharmacokinetic properties of chemicals are affected by the route of administration and these may affect the absorption rate. Models have been developed to simplify conceptualization of the processes that take place in the interaction between an organism and a chemical substance. The various compartments that the model is divided into are commonly referred to as the ADME scheme, absorption - the process of a substance entering the blood circulation. Distribution - the dispersion or dissemination of substances throughout the fluids, metabolism – the recognition by the organism that a foreign substance is present and the irreversible transformation of parent compounds into daughter metabolites. Excretion - the removal of the substances from the body, in rare cases, some drugs irreversibly accumulate in body tissue. The two phases of metabolism and excretion can also be grouped together under the title elimination, the study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. All these concepts can be represented through mathematical formulas that have a graphical representation. The model outputs for a drug can be used in industry or in the application of pharmacokinetic concepts. Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals, in practice, it is generally considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph, compartmental methods estimate the concentration-time graph using kinetic models. Noncompartmental methods are more versatile in that they do not assume any specific compartmental model. The final outcome of the transformations that a drug undergoes in an organism, a number of functional models have been developed in order to simplify the study of pharmacokinetics. These models are based on a consideration of an organism as a number of related compartments, the simplest idea is to think of an organism as only one homogenous compartment. However, these models do not always reflect the real situation within an organism
4.
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
5.
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
6.
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
7.
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
8.
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
9.
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
10.
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
11.
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
12.
Serotonin
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Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is found in the gastrointestinal tract, blood platelets. It is popularly thought to be a contributor to feelings of well-being, approximately 90% of the human bodys total serotonin is located in the enterochromaffin cells in the GI tract, where it is used to regulate intestinal movements. The remainder is synthesized in serotonergic neurons of the CNS, where it has various functions and these include the regulation of mood, appetite, and sleep. Serotonin also has some functions, including memory and learning. Modulation of serotonin at synapses is thought to be an action of several classes of pharmacological antidepressants. Serotonin secreted from the cells eventually finds its way out of tissues into the blood. There, it is taken up by blood platelets, which store it. When the platelets bind to a clot, they release serotonin, Serotonin is also a growth factor for some types of cells, which may give it a role in wound healing. Serotonin is metabolized mainly to 5-HIAA, chiefly by the liver, metabolism involves first oxidation by monoamine oxidase to the corresponding aldehyde. This is followed by oxidation by aldehyde dehydrogenase to 5-HIAA, the acetic acid derivative. The latter is then excreted by the kidneys, in addition to animals, serotonin is found in fungi and plants. Serotonins presence in insect venoms and plant spines serves to cause pain, Serotonin is produced by pathogenic amoebae, and its effect on the gut causes diarrhea. Its widespread presence in many seeds and fruits may serve to stimulate the digestive tract into expelling the seeds, Serotonin is a neurotransmitter and is found in all bilateral animals, where it mediates gut movements and the animals perceptions of resource availability. In less complex animals, such as invertebrates, resources simply mean food availability. In more complex animals, such as arthropods and vertebrates, resources also can mean social dominance, in response to the perceived abundance or scarcity of resources, an animals growth, reproduction or mood may be elevated or lowered. This may somewhat depend on how much serotonin the organism has at its disposal, except for the 5-HT3 receptor, a ligand-gated ion channel, all other 5-HT receptors are G-protein-coupled receptors that activate an intracellular second messenger cascade. Serotonergic action is terminated primarily via uptake of 5-HT from the synapse and this is accomplished through the specific monoamine transporter for 5-HT, SERT, on the presynaptic neuron
13.
Enantiomer
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A single chiral atom or similar structural feature in a compound causes that compound to have two possible structures which are non-superposable, each a mirror image of the other. Each member of the pair is termed an enantiomorph, the property is termed enantiomerism. The presence of multiple features in a given compound increases the number of geometric forms possible. Enantiopure compounds refer to samples having, within the limits of detection and they are sometimes called optical isomers for this reason. Enantiomer members often have different chemical reactions with other enantiomer substances, since many biological molecules are enantiomers, there is sometimes a marked difference in the effects of two enantiomers on biological organisms. Owing to this discovery, drugs composed of one enantiomer can be developed to enhance the pharmacological efficacy. An example is eszopiclone, which is enantiopure and therefore administered in doses that are exactly 1/2 of the older, in the case of eszopiclone, the S enantiomer is responsible for all the desired effects, while the other enantiomer seems to be inactive. A dose of 2 mg of zopiclone must be administered to produce the therapeutic effect as 1 mg of eszopiclone. In chemical synthesis of enantiomeric substances, non-enantiomeric precursors inevitably produce racemic mixtures, in the absence of an effective enantiomeric environment, separation of a racemic mixture into its enantiomeric components is impossible. The R/S system is an important nomenclature system for denoting distinct enantiomers, another system is based on prefix notation for optical activity, - and - or d- and l-. The Latin for left and right is laevus and dexter, respectively, left and right have always had moral connotations, and the Latin words for these are sinister and rectus. The English word right is a cognate of rectus and this is the origin of the D, L and S, R notations, and the employment of prefixes levo- and dextro- in common names. Most compounds that one or more asymmetric carbon atoms show enantiomerism. There are a few compounds that do have asymmetric carbon atoms. An example of such an enantiomer is the sedative thalidomide, which was sold in a number of countries across the world from 1957 until 1961 and it was withdrawn from the market when it was found to cause of birth defects. One enantiomer caused the desirable effects, while the other, unavoidably present in equal quantities. The herbicide mecoprop is a mixture, with the --enantiomer possessing the herbicidal activity. Another example is the antidepressant drugs escitalopram and citalopram, citalopram is a racemate, escitalopram is a pure enantiomer
14.
Fenfluramine
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Fenfluramine, also known as 3-trifluoromethyl-N-ethylamphetamine, is an anorectic that is no longer marketed. In combination with phentermine, it was part of the anti-obesity medication Fen-phen, Fenfluramine was introduced on the U. S. market in 1973 and withdrawn in 1997. It is the mixture of two enantiomers, dexfenfluramine and levofenfluramine. The drug increases the level of serotonin, a neurotransmitter that regulates mood, appetite, Fenfluramine causes the release of serotonin by disrupting vesicular storage of the neurotransmitter, and reversing serotonin transporter function. The result is a feeling of fullness and reduced appetite, the drug was withdrawn from the U. S. market in 1997 after reports of heart valve disease and pulmonary hypertension, including a condition known as cardiac fibrosis. It was subsequently withdrawn from markets around the world. It was banned in India in 1998, the distinctive valvular abnormality seen with fenfluramine is a thickening of the leaflet and chordae tendineae. One mechanism used to explain this phenomenon involves heart valve serotonin receptors, since fenfluramine and its active metabolite norfenfluramine stimulate serotonin receptors, this may have led to the valvular abnormalities found in patients using fenfluramine. In particular norfenfluramine is a potent inhibitor of the re-uptake of 5-HT into nerve terminals, Fenfluramine and its active metabolite norfenfluramine affect the 5-HT2B receptors which are plentiful in human cardiac valves. The suggested mechanism by which fenfluramine causes damage is through over or inappropriate stimulation of these leading to inappropriate valve cell division. Supporting this idea is the fact that this valve abnormality has also occurred in patients using other drugs that act on 5-HT2B receptors, according to a study of 5743 former users conducted by a plaintiffs expert cardiologist, damage to the heart valve continued long after stopping the medication. Of the users tested,20 percent of women, and 12 percent of men were affected, for all ex-users, there was a sevenfold increase of chances of needing surgery for faulty heart valves caused by the drug. There have been reports associating fenfluramine with depression, psychosis, exacerbation of pre-existing psychosis and these effects may be mediated by serotonergic neurotoxicity/depletion of serotonin with chronic administration and/or activation 5-HT2A receptors. In overdose, fenfluramine can result in serotonin syndrome and death, unlike various other amphetamine derivatives, fenfluramine is reported to be dysphoric, unpleasantly lethargic, and non-addictive. At high doses, fenfluramine induces a state resembling that produced by lysergic acid diethylamide. Prepn, L. G. Beregi et al, prepn of optical isomers, eidem, US3198834. Benfluorex Tiflorex Welch, J. T. Lim, D. S, the Synthesis and Biological Activity of Pentafluorosulfanyl Analogs of Fluoxetine, Fenfluramine, and Norfenfluramine. RxList. com - Fenfluramine Inchem. org - Fenfluramine circ. ahajournals. org
15.
Amphetamine
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Amphetamine is a potent central nervous system stimulant that is used in the treatment of attention deficit hyperactivity disorder, narcolepsy, and obesity. Amphetamine was discovered in 1887 and exists as two enantiomers, levoamphetamine and dextroamphetamine, amphetamine properly refers to a specific chemical, the racemic free base, which is equal parts of the two enantiomers, levoamphetamine and dextroamphetamine, in their pure amine forms. The term is used informally to refer to any combination of the enantiomers. Historically, it has used to treat nasal congestion and depression. Amphetamine is also used as a performance enhancer and cognitive enhancer. The first amphetamine pharmaceutical was Benzedrine, a brand which was used to treat a variety of conditions, currently, pharmaceutical amphetamine is prescribed as racemic amphetamine, Adderall, dextroamphetamine, or the inactive prodrug lisdexamfetamine. At therapeutic doses, amphetamine causes emotional and cognitive effects such as euphoria, change in desire for sex, increased wakefulness and it induces physical effects such as decreased reaction time, fatigue resistance, and increased muscle strength. Larger doses of amphetamine may impair cognitive function and induce rapid muscle breakdown, drug addiction is a serious risk with large recreational doses but is unlikely to arise from typical long-term medical use at therapeutic doses. Very high doses can result in psychosis which rarely occurs at therapeutic doses even during long-term use, recreational doses are generally much larger than prescribed therapeutic doses and carry a far greater risk of serious side effects. Amphetamine belongs to the phenethylamine class and it is also the parent compound of its own structural class, the substituted amphetamines, which includes prominent substances such as bupropion, cathinone, MDMA, and methamphetamine. Phenethylamine is the parent compound of amphetamine, while N-methylphenethylamine is an isomer of amphetamine that differs only in the placement of the methyl group. Amphetamine is used to attention deficit hyperactivity disorder, narcolepsy, and obesity. Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD, randomized controlled trials of continuous stimulant therapy for the treatment of ADHD spanning two years have demonstrated treatment effectiveness and safety. Psychostimulants like methylphenidate and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems, approximately 80% of those who use these stimulants see improvements in ADHD symptoms. A systematic review from 2014 found that low doses of amphetamine also improve memory consolidation, therapeutic doses of amphetamine also enhance cortical network efficiency, an effect which mediates improvements in working memory in all individuals. Amphetamine and other ADHD stimulants also improve task saliency and increase arousal, stimulants such as amphetamine can improve performance on difficult and boring tasks and are used by some students as a study and test-taking aid. However, high doses that are above the therapeutic range can interfere with working memory. Amphetamine improves endurance and reaction time primarily through reuptake inhibition and effluxion of dopamine in the nervous system
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Food and Drug Administration
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The Food and Drug Administration is a federal agency of the United States Department of Health and Human Services, one of the United States federal executive departments. As of 2017, 3/4th of the FDA budget is funded by the pharmaceutical companies due to the Prescription drug user fee act and these include regulating lasers, cellular phones, condoms and control of disease on products ranging from certain household pets to sperm donation for assisted reproduction. The FDA is led by the Commissioner of Food and Drugs, appointed by the President with the advice, the Commissioner reports to the Secretary of Health and Human Services. Dr. Robert M. Califf, MD is the current commissioner, who took over in February 2016 for Dr. Stephen Ostroff, the FDA has its headquarters in unincorporated White Oak, Maryland. The agency also has 223 field offices and 13 laboratories located throughout the 50 states, the United States Virgin Islands, in 2008, the FDA began to post employees to foreign countries, including China, India, Costa Rica, Chile, Belgium, and the United Kingdom. The site was renamed from the White Oak Naval Surface Warfare Center to the Federal Research Center at White Oak, the first building, the Life Sciences Laboratory, was dedicated and opened with 104 employees on the campus in December 2003. Only one original building from the facility was kept. All other buildings are new construction, the project is slated to be completed by 2017, assuming future Congressional funding While most of the Centers are located in the Washington, D. C. The Office of Regulatory Affairs is considered the eyes and ears of the agency, the Office of Regulatory Affairs is divided into five regions, which are further divided into 20 districts. Districts are based roughly on the divisions of the federal court system. Each district comprises a main office and a number of Resident Posts. ORA also includes the Agencys network of laboratories, which analyze any physical samples taken. Though samples are usually food-related, some laboratories are equipped to analyze drugs, cosmetics, the Office of Criminal Investigations was established in 1991 to investigate criminal cases. Unlike ORA Investigators, OCI Special Agents are armed, and dont focus on aspects of the regulated industries. In many cases, OCI pursues cases involving Title 18 violations, OCI Special Agents often come from other criminal investigations backgrounds, and work closely with the Federal Bureau of Investigation, Assistant Attorney General, and even Interpol. OCI receives cases from a variety of sources—including ORA, local agencies, OCI is a smaller branch, comprising about 200 agents nationwide. The FDA frequently works with federal agencies, including the Department of Agriculture, Drug Enforcement Administration, Customs and Border Protection. Often local and state government agencies also work with the FDA to provide regulatory inspections, the FDA regulates more than US$1 trillion worth of consumer goods, about 25% of consumer expenditures in the United States
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Massachusetts Institute of Technology
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The Massachusetts Institute of Technology is a private research university in Cambridge, Massachusetts, often cited as one of the worlds most prestigious universities. Researchers worked on computers, radar, and inertial guidance during World War II, post-war defense research contributed to the rapid expansion of the faculty and campus under James Killian. The current 168-acre campus opened in 1916 and extends over 1 mile along the bank of the Charles River basin. The Institute is traditionally known for its research and education in the sciences and engineering, and more recently in biology, economics, linguistics. Air Force and 6 Fields Medalists have been affiliated with MIT, the school has a strong entrepreneurial culture, and the aggregated revenues of companies founded by MIT alumni would rank as the eleventh-largest economy in the world. In 1859, a proposal was submitted to the Massachusetts General Court to use newly filled lands in Back Bay, Boston for a Conservatory of Art and Science, but the proposal failed. A charter for the incorporation of the Massachusetts Institute of Technology, Rogers, a professor from the University of Virginia, wanted to establish an institution to address rapid scientific and technological advances. The Rogers Plan reflected the German research university model, emphasizing an independent faculty engaged in research, as well as instruction oriented around seminars, two days after the charter was issued, the first battle of the Civil War broke out. After a long delay through the war years, MITs first classes were held in the Mercantile Building in Boston in 1865, in 1863 under the same act, the Commonwealth of Massachusetts founded the Massachusetts Agricultural College, which developed as the University of Massachusetts Amherst. In 1866, the proceeds from sales went toward new buildings in the Back Bay. MIT was informally called Boston Tech, the institute adopted the European polytechnic university model and emphasized laboratory instruction from an early date. Despite chronic financial problems, the institute saw growth in the last two decades of the 19th century under President Francis Amasa Walker. Programs in electrical, chemical, marine, and sanitary engineering were introduced, new buildings were built, the curriculum drifted to a vocational emphasis, with less focus on theoretical science. The fledgling school still suffered from chronic financial shortages which diverted the attention of the MIT leadership, during these Boston Tech years, MIT faculty and alumni rebuffed Harvard University president Charles W. Eliots repeated attempts to merge MIT with Harvard Colleges Lawrence Scientific School. There would be at least six attempts to absorb MIT into Harvard, in its cramped Back Bay location, MIT could not afford to expand its overcrowded facilities, driving a desperate search for a new campus and funding. Eventually the MIT Corporation approved an agreement to merge with Harvard, over the vehement objections of MIT faculty, students. However, a 1917 decision by the Massachusetts Supreme Judicial Court effectively put an end to the merger scheme, the neoclassical New Technology campus was designed by William W. Bosworth and had been funded largely by anonymous donations from a mysterious Mr. Smith, starting in 1912. In January 1920, the donor was revealed to be the industrialist George Eastman of Rochester, New York, who had invented methods of production and processing
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Wyeth
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Wyeth was a pharmaceutical company purchased by Pfizer in 2009. The company was founded in Philadelphia, Pennsylvania, in 1860 as John Wyeth and it was later known as American Home Products before being renamed to Wyeth in 2002. Its headquarters moved to Collegeville, Pennsylvania, and Madison, New Jersey, the infant and maternal nutrition business was acquired by Nestlé in 2012. Wyeth manufactured over-the-counter drugs Robitussin and the analgesic Advil as well as prescription drugs Premarin, in 1860, pharmacists John and Frank Wyeth opened a drugstore with a small research lab on Walnut Street in Philadelphia. In 1862, on the suggestion of doctors, they began to manufacture quantities of commonly ordered medicines. They were successful, and in 1864 they began supplying medicines, in 1872, Henry Bowers, an employee of Wyeth, developed one of the first rotary compressed tablet machines in the United States. This enabled the production of medicines with unprecedented precision and speed. It was successful, and the Wyeth brothers won awards at the Centennial Exhibition. In 1883, Wyeth opened its first international facility in Montreal, Canada, six years later a fire destroyed the brothers original Walnut Street store, and they sold the retail business and focused on mass production. Cobalt blue glass bottles embossed with either Wyeth or John Wyeth & Brother in the glass are among the most popular antique bottles sought after by collectors, John Wyeth died in 1907 and his only son, Stuart, became the companys president. The Whitehall building in downtown Manhattan became the corporations first headquarters, global sales increased due to the sales of Wyeths Kolynos brand of toothpaste. In 1929, Stuart Wyeth died and left controlling interest to Harvard University, in 1930, Wyeth purchased Anacin, a product for tension headaches which quickly became the companys flagship product. One year later, Harvard sold Wyeth to American Home Products for US$2.9 million, in 1935, Alvin G. Brush, a Certified Public Accountant, became CEO of the organization and served for 30 years. Under Brushs leadership,34 new companies were acquired in 15 years, including Chef Boyardee, corporation, a pharmaceutical firm specializing in infant formulas. Wyeth also made its first licensing deal, acquiring an antibiotic for arthritis vaccine research, in 1941, the US entered World War II, and AHP shipped typical wartime drugs such as sulfa bacteriostatics, blood plasma, typhus vaccine, quinine, and atabrine tablets. Wyeth was later rewarded for its contribution to the war effort, during this time, Wyeth launched its penicillin research facility with G. Raymond Rettew. In 1943, Wyeth purchased G. Washington Coffee Refining Company, in 1943, AHP merged with Ayerst, McKenna and Harrison, Ltd. of Canada. AHP was one of 22 companies selected by the government in 1944 to manufacture penicillin for the military, in 1945, AHP acquired the Fort Dodge Serum Company, entering the animal health field
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Levofenfluramine
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Levofenfluramine, or -3-trifluoromethyl-N-ethylamphetamine, also known as -fenfluramine or -fenfluramine, is a drug of the amphetamine family that, itself, was never marketed. It is the enantiomer of fenfluramine, the racemic form of the compound. Both fenfluramine and dexfenfluramine are anorectic agents that have been used clinically in the treatment of obesity, contrarily, levofenfluramine is thought to contribute only to unwanted side effects. Of course, this is speculation and has not been proven. As such, likely contributes significantly to the biological activity—though not necessarily appetite suppressant effects—of not only levofenfluramine, in contrast to levonorfenfluramine, levofenfluramine is virtually inactive as a reuptake inhibitor or releaser of norepinephrine, and neither compound has any effect on dopamine reuptake or release
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Benfluorex
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Benfluorex is an anorectic and hypolipidemic agent that is structurally related to fenfluramine patented and manufactured by a French pharmaceutical company Servier. Two clinical studies have shown it may improve glycemic control and decrease insulin resistance in people with poorly controlled type 2 diabetes, however, Servier is suspected of having marketed Mediator at odds with the drugs medical properties. Thus Frachon et al. showed a higher prevalence of unexplained valvular heart disease in patients taking benfluorex compared to controls. And Weill et al. looked at over 1 million diabetic patients demonstrating a higher rate in benfluorex takers for valvular heart disease. In France the medication had been marketed as by Servier as an adjuvant antidiabetic under the name Mediator, the drug was on the market between 1976 and 2009 and is thought to have caused between 500 –2,000 deaths. The drug was used in Spain, Portugal and Cyprus. Fenfluramine, a drug, had been withdrawn from the market in 1997 after reports of heart valve disease, pulmonary hypertension. Both fenfluramine and benfluorex form norfenfluramine as a metabolite and this side effect led to the withdrawal of fenfluramine as an anorectic drug worldwide, and later to the withdrawal of benfluorex in Europe. Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, evidence for possible involvement of 5-HT receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications
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Fenfluramine/phentermine
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The drug combination fenfluramine/phentermine, usually called fen-phen, was an anti-obesity treatment that utilized two anorectics. Phentermine was not shown to have harmful effects, fenfluramine acts as a serotonin releasing agent, phentermine as a norepinephrine, dopamine and serotonin releasing agent. Fenfluramine as a drug was first introduced in the 1970s. A1984 study found a loss of 7.5 kg on average in 24 weeks. It sold modestly until the 1990s, when it was combined with phentermine, a similar drug, aminorex, had caused severe lung damage and provided reason to worry that similar drugs. Could increase the risk of a rare but often fatal lung disease, in 1995, Wyeth introduced dexfenfluramine, which it hoped would cause fewer adverse effects. However, the officer of the Food and Drug Administration, Leo Lutwak. After Lutwak refused to approve the drug, the FDA management had someone else sign it, european regulators required a major warning of pulmonary hypertension risks. In 1996, a paper in the New England Journal of Medicine from the Mayo Clinic discussed clinical findings in 24 people who had taken fen-phen, the authors noted that their findings suggested a possible correlation between mitral valve dysfunction and the use of these anorectic agents. Later in 1996, a 30-year-old woman developed heart problems after a month of using it, when she died in February 1997, the FDA subsequently received over a hundred additional reports of valvular heart disease in people taking fen-phen, fenfluramine alone or dexfenfluramine alone. The FDA requested that the manufacturers of fenfluramine and dexfenfluramine stress the risk to the heart in the drugs labeling. As of 1997, the FDA was continuing to receive reports of heart disease in persons who had taken these drugs. This disease typically involves the aortic and mitral valves, the action was based on findings from doctors who had evaluated people taking these two drugs with echocardiograms, a procedure that can test the functioning of heart valves. The findings indicated that approximately 30 percent of people who had taken the combination up to 24 months had abnormal echocardiograms, even though they had no symptoms. This percentage of abnormal test results was much higher than would be expected from a comparatively sized sample of the population who had not been exposed to either fenfluramine or dexfenfluramine. Follow up studies showed that for people who took the combination for 3 months or less, fen-phen is no longer widely available. In April 2005, American Lawyer magazine ran a story on the wave of fen-phen litigation. Estimates of total liability ran as high as $14 billion, one plaintiffs attorney claimed that the payments not going to be large enough to cover medical expenses
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Anti-obesity medication
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Anti-obesity medication or weight loss drugs are all pharmacological agents that reduce or control weight. These drugs alter one of the processes of the human body, weight regulation, by altering either appetite. The main treatment modalities for overweight and obese individuals remain dieting, in the United States orlistat is currently approved by the FDA for long-term use. It reduces intestinal fat absorption by inhibiting pancreatic lipase, rimonabant, a second drug, works via a specific blockade of the endocannabinoid system. It has been developed from the knowledge that cannabis smokers often experience hunger and it had been approved in Europe for the treatment of obesity but has not received approval in the United States or Canada due to safety concerns. The European Medicines Agency in October 2008 recommended the suspension of the sale of rimonabant as the risks seem to be greater than the benefits, drugs blocking the cannabinoid receptors may be a future strategy for appetite suppression. Interference with the ability to absorb specific nutrients in food. For example, Orlistat blocks fat breakdown and thereby prevents fat absorption, the first described attempts at producing weight loss are those of Soranus of Ephesus, a Greek physician, in the second century AD. He prescribed elixirs of laxatives and purgatives, as well as heat, massage and this remained the mainstay of treatment for well over a thousand years. It was not until the 1920s and 1930s that new treatments began to appear, based on its effectiveness for hypothyroidism, thyroid hormone became a popular treatment for obesity in euthyroid people. It had a modest effect but produced the symptoms of hyperthyroidism as an effect, such as palpitations. 2, 4-Dinitrophenol was introduced in 1933, this worked by uncoupling the biological process of oxidative phosphorylation in mitochondria, the most significant side effect was a sensation of warmth, frequently with sweating. Overdose, although rare, lead to a rise in temperature and, ultimately. By the end of 1938 DNP had fallen out of use because the FDA had become empowered to put pressure on manufacturers, amphetamines became popular for weight loss during the late 1930s. They worked primarily by suppressing appetite, and had other effects such as increased alertness. Use of amphetamines increased over the subsequent decades, including Obetrol and this was a combination of multiple pills, all thought to help with weight loss, taken throughout the day. Typical regimens included stimulants, such as amphetamines, as well as thyroid hormone, diuretics, digitalis, laxatives, in 1967/1968 a number of deaths attributed to diet pills triggered a Senate investigation and the gradual implementation of greater restrictions on the market. Meanwhile, phentermine had been FDA approved in 1959 and fenfluramine in 1973, the two were no more popular than other drugs until in 1992 a researcher reported that when combined the two caused a 10% weight loss which was maintained for more than two years
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Stimulant
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Stimulants is an overarching term that covers many drugs including those that increase activity of the body, drugs that are pleasurable and invigorating, or drugs that have sympathomimetic effects. Due to their rendering a characteristic up feeling, stimulants are also referred to as uppers. Depressants or downers, which decrease mental and/or physical function, are in stark contrast to stimulants and are considered to be the functionally opposite drug class, Stimulants are widely used throughout the world as prescription medicines as well as without a prescription as performance-enhancing or recreational drugs. The most frequently prescribed stimulants as of 2013 were lisdexamfetamine, methylphenidate and it is estimated that the percent of the population that has abused amphetamines, cocaine and MDMA combined is between. 8% and 2. 1%. Stimulants in therapeutic doses, such as given to patients with ADHD, increases ability to focus, vigor, sociability, libido. However, in higher doses stimulants may actually decrease the ability to focus, in higher doses stimulants may also produce euphoria, vigor, and decrease need for sleep. Many, but not all, stimulants have ergogenic effects, Drugs such as ephedrine, pseudoephedrine, amphetamine and methylphenidate have well documented ergogenic effects, while drugs such as cocaine and methamphetamine have the opposite effect. In some cases psychiatric phenomenon may emerge such as stimulant psychosis, paranoia, acute toxicity has been reportedly associated with a homicide, paranoia, aggressive behavior, motor dysfunction, and punding. The violent and aggressive behavior associated with acute stimulant toxicity may partially be driven by paranoia, most drugs classified as stimulants are sympathomimetics, that is they stimulate the sympathetic branch of the autonomic nervous system. This leads to such as mydriasis, increased heart rate, blood pressure, respiratory rate. When these changes become pathological, they are called arrhythmia, hypertension, and hyperthermia, however given the complexity of the mechanisms that underly these potentially fatal outcomes of acute stimulant toxicity, it is impossible to determine what dose may be lethal. Assessment of the effects of stimulants is relevant given the large population currently taking stimulants. A systematic review of cardiovascular effects of prescription stimulants found no association in children, a review over a four-year period found that there were few negative effects of stimulant treatment, but stressed the need for longer term studies. A review of a long period of prescription stimulate use in those with ADHD found that cardiovascular side effects were limited to transient increases in blood pressure only. Initiation of stimulant treatment in those with ADHD in early childhood appears to carry benefits into adulthood with regard to social and cognitive functioning, Abuse of prescription stimulants or of illicit stimulants carries many negative health risks. Abuse of cocaine, depending upon route of administration, increases risk of disease, stroke. Cocaine may also increase risk for disease, as well as damage nasal cartilage. Abuse of methamphetamine produces similar effects as well as marked degeneration of dopaminergic neurons, Drugs used to treat sleep disorders such as excessive daytime sleepiness are called eugeroics, and include notable stimulants such as modafinil
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4-Methylamphetamine
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4-Methylamphetamine is a stimulant and anorectic drug of the phenethylamine and amphetamine chemical classes. However, more recent in vivo studies that involved performing microdialysis on rats showed a different trend and these studies showed that 4-methylamphetamine is much more potent at elevating serotonin relative to dopamine. The authors speculated that this is because 5-HT release dampens DA release through some mechanism, for example, it was suggested that a possible cause for this could be activation of 5HT2C receptors since this is known to inhibit DA release. In addition there are alternative explanations such as 5-HT release then going on to encourage GABA release, 4-MA was investigated as an appetite suppressant in 1952 and was even given a trade name, Aptrol, but development was apparently never completed. More recently it has reported as a novel designer drug. More than a dozen deaths have been reported throughout Europe in 2012-2013 after consumption of amphetamine contaminated with 4-methylamphetamine, since 4-MA has little, if any, desirable psychoactive properties, researchers doubt the substance was sold as amphetamine on purpose. A contaminated precursor, after yielding a mixture of amphetamine and 4-MA. 1--2-aminobutane 2-Methylamphetamine 3-Methylamphetamine 4-Methyl-N-methylamphetamine 4-Methyl-N-methylcathinone 3-Methoxy-4-methylamphetamine 3, 4-Dimethylamphetamine
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Aminorex
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Aminorex is a weight loss stimulant drug. It was withdrawn from the market after it was found to cause pulmonary hypertension, in the U. S. it is an illegal Schedule I drug, with no medical use and poor safety profile. Aminorex, in the 2-amino-5-aryl oxazoline class, was developed by McNeil in 1962 and it is closely related to 4-methylaminorex. Aminorex has been shown to have locomotor stimulant effects, lying midway between dextroamphetamine and methamphetamine, aminorex effects have been attributed to the release of catecholamines. It was discovered in 1962 by Edward John Hurlburt, and was found in 1963 to have an anorectic effect in rats. The racemic synthesis involves addition/cyclization reaction of 2-amino-1-phenylethanol with cyanogen bromide, a similar synthesis has been also published. 4-Methylaminorex Clominorex Cyclazodone Fenozolone Fluminorex Pemoline Thozalinone
