The κ-opioid receptor is a G protein-coupled receptor that in humans is encoded by the OPRK1 gene. The KOR is coupled to the G protein Gi/G0 and is one of four related receptors that bind opioid-like compounds in the brain and are responsible for mediating the effects of these compounds; these effects include altering nociception, motor control, mood. Dysregulation of this receptor system has been implicated in drug addiction; the KOR is a type of opioid receptor that binds the opioid peptide dynorphin as the primary endogenous ligand. In addition to dynorphin, a variety of natural alkaloids and other synthetic ligands bind to the receptor; the KOR may provide a natural addiction control mechanism, therefore, drugs that target this receptor may have therapeutic potential in the treatment of addiction. There is evidence. KORs are distributed in the brain, spinal cord, in peripheral tissues. High levels of the receptor have been detected in the prefrontal cortex, periaqueductal gray, raphe nuclei, ventral tegmental area, substantia nigra, dorsal striatum, ventral striatum, bed nucleus stria terminalis, hippocampus, midline thalamic nuclei, locus coeruleus, spinal trigeminal nucleus, parabrachial nucleus, solitary nucleus.
Based on receptor binding studies, three variants of the KOR designated κ1, κ2, κ3 have been characterized. However, only one cDNA clone has been identified, hence these receptor subtypes arise from interaction of one KOR protein with other membrane associated proteins. To μ-opioid receptor agonists, KOR agonists are potently analgesic, have been employed clinically in the treatment of pain. However, KOR agonists produce side effects such as dysphoria and dissociation, which has limited their clinical usefulness. Examples of KOR agonists that have been used medically as analgesics include butorphanol, levorphanol, pentazocine and eptazocine. Difelikefalin and CR665 are peripherally restricted KOR agonists lacking the CNS side effects of centrally active KOR agonists and are under clinical investigation as analgesics. Centrally active KOR agonists have hallucinogenic or dissociative effects, as exemplified by salvinorin A; these effects are undesirable in medicinal drugs. It is thought that the hallucinogenic and dysphoric effects of opioids such as butorphanol and pentazocine serve to limit their abuse potential.
In the case of salvinorin A, a structurally novel neoclerodane diterpene KOR agonist, these hallucinogenic effects are sought after though the experience is considered dysphoric by the user. While salvinorin A is considered a hallucinogen, its effects are qualitatively different than those produced by the classical psychedelic hallucinogens such as lysergic acid diethylamide, psilocybin, or mescaline; the claustrum is the region of the brain. It has been proposed that this area, based on its structure and connectivity, has "a role in coordinating a set of diverse brain functions", the claustrum has been elucidated as playing a crucial role in consciousness; as examples, lesions of the claustrum in humans are associated with disruption of consciousness and cognition, electrical stimulation of the area between the insula and the claustrum has been found to produce an immediate loss of consciousness in humans along with recovery of consciousness upon cessation of the stimulation. On the basis of the preceding knowledge, it has been proposed that inhibition of the claustrum by activation of KORs in these areas is responsible for the profound consciousness-altering/dissociative hallucinogen effects of salvinorin A and other KOR agonists.
In addition, it has been stated that "the subjective effects of S. divinorum indicate that salvia disrupts certain facets of consciousness much more than the serotonergic hallucinogen ", it has been postulated that inhibition of a brain area, as fundamentally involved in consciousness and higher cognitive function as the claustrum may explain this. However, these conclusions are tentative, as " are not exclusive to the claustrum. In supplementation of the above, according to Addy et al.: Theories suggest the claustrum may act to bind and integrate multisensory information, or else to encode sensory stimuli as salient or nonsalient. One theory suggests the claustrum harmonizes and coordinates activity in various parts of the cortex, leading to the seamless integrated nature of subjective conscious experience. Disrupting claustral activity may lead to conscious experiences of disintegrated or unusually bound sensory information including synesthesia; such theories are in part corroborated by the fact that, which functions exclusively on the KOR system, can cause consciousness to be decoupled from external sensory input, leading to experiencing other environments and locations, perceiving other “beings” besides those in the room, forgetting oneself and one’s body in t
2C-B-FLY is a psychedelic phenethylamine of the 2C family. It was first synthesized in 1996 by Aaron P. Monte. 2C-B-FLY is 8-bromo-2,3,6,7-benzo-dihydro-difuran-ethylamine. The full name of the chemical is 2-ethanamine, it has been subject to little formal study, but its appearance as a designer drug has led the DEA to release analytical results for 2C-B-FLY and several related compounds. In theory, dihydrodifuran analogues of any of the 2Cx / DOx family of drugs could be made, would be expected to show similar activity to the parent compound. So in the same way that 2C-B-FLY is the dihydrodifuran analogue of 2C-B, the 8-iodo equivalent 2C-I-FLY would be the dihydrodifuran analogue of 2C-I, the 8-methyl equivalent 2C-D-FLY would be the dihydrodifuran analogue of 2C-D. Other related compounds can be produced, where the alpha carbon of the ethylamine chain is methylated, the amphetamine derivative DOB-FLY can be made, this compound being the dihydrodifuran analogue of DOB, or conversely can be viewed as the saturated derivative of Bromo-DragonFLY.
Where only one methoxy group of a 2Cx drug is cyclised into a dihydrofuran ring, the resulting compound is known as a "hemifly", when an unsaturated furan ring is used, the compound is known as a "hemi-dragonfly". The larger saturated hexahydrobenzodipyran ring derivatives have been referred to as "butterfly" compounds; the 8-bromo group can be replaced by other 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 have two possible positional isomers, with different potencies at the various 5-HT2 subtypes. Isomeric "Ψ"-derivatives with the oxygens positioned at the 2,6- positions, mescaline analogues with the oxygens at 3,5- have been made, but both are less potent than the corresponding 2,5- isomers; the symmetrical aromatic benzodifuran derivatives tend to have the highest binding affinity at 5-HT2A, but the saturated benzodifuran derivatives have higher efficacy, while the saturated benzodipyran derivatives are more selective for 5-HT2C.
A large number of possible combinations have been synthesised and tested for activity, but these represent only a fraction of the many variations that could be produced. Alexander Shulgin lists a dosage of 2C-B-FLY at 10 mg orally; the toxicity of 2C-B-FLY in humans is unknown. Two deaths occurred in October 2009, in Denmark and the United States, after ingestion of a substance, sold as 2C-B-FLY a small-time RC shop, but in fact consisted of Bromo-DragonFLY contaminated with a small amount of unidentified impurities; as of October 31, 2016. 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; the hallucinogenic effect of 2C-B-FLY is mediated by its partial agonistic activity at the 5-HT2A serotonin receptor, but has a high binding affinity for the 5-HT1D, 5-HT1E, 5-HT1A, 5-HT2B and 5-HT2C receptors.
2C-B-FLY Entry at Erowid 2C-B-FLY Entry at Isomerdesign
The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1
A hallucinogen is a psychoactive agent which can cause hallucinations, perceptual anomalies, other substantial subjective changes in thoughts and consciousness. The common types of hallucinogens are psychedelics 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 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 to the same substance.'Hallucinations' and'psychedelia' may both refer to the same aspects of subjective experience in a given instance.
The term psychedelia carries an added reference to psychedelic substance culture, and'psychedelics' are considered by many to be the'traditional' or'classical hallucinogens' including DMT, Psilocybin, LSD.'A hallucinogen' in this sense broadly refers to any substance which causes changes in perception or hallucinations, while psychedelics carry a positive connotation of general perceptual enhancement. In contrast to Hollister's 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. It is applied to any drug with perception-altering effects such as LSD and other ergotamine derivatives, DMT and other tryptamines including the alkaloids of Psilocybe spp. mescaline and other phenethylamines. The term "psychedelic" is applied somewhat interchangeably with "psychotomimetic" and "hallucinogen", The classical hallucinogens are considered to be the representative psychedelics and LSD is considered the prototypical psychedelic.
In order to refer to the LSD-like psychedelics, scientific authors have used the term "classical hallucinogen" in the sense defined by Glennon: "The classical hallucinogens are agents that meet Hollister's original definition, but are agents that: bind at 5-HT2 serotonin receptors, are recognized by animals trained to discriminate 1--2-aminopropane from vehicle. Otherwise, when the term "psychedelic" is used to refer only to the LSD-like psychedelics, authors explicitly point that they intend "psychedelic" to be understood according to this more restrictive interpretation. One explanatory model for the experiences provoked by psychedelics is the "reducing valve" concept, first articulated in Aldous Huxley's book The Doors of Perception. In this view, the drugs disable the brain's "filtering" ability to selectively prevent certain perceptions, emotions and thoughts from reaching the conscious mind; this effect has been described as mind expanding, or consciousness expanding, for the drug "expands" the realm of experience available to conscious awareness.
While possessing a unique mechanism of action, cannabis or marijuana has been regarded alongside the classic psychedelics. A designer drug is a structural or functional analog of a controlled substance, designed to mimic the pharmacological effects of the original drug while at the same time avoid being classified as illegal and/or avoid detection in standard drug tests. Many designer drugs and research chemicals are hallucinogenic in nature, such as those in the 2C and 25-NB families. Dissociatives produce analgesia and catalepsy at anesthetic doses, they produce a sense of detachment from the surrounding environment, hence "the state has been designated as dissociative anesthesia since the patient seems disassociated from his environment." Dissociative symptoms include the disruption or compartmentalization of "...the integrated functions of consciousness, identity or perception."p. 523 Dissociation of sensory input can cause derealization, the perception of the outside world as being dream-like or unreal.
Other dissociative experiences include depersonalization, which includes feeling detached from one's body. Simeon offered "...common descriptions of depersonalisation experiences: watching oneself from a distance. However, dissociation is remarkably administered by salvinorin A's potent κ-opioid receptor agonism, though sometimes described as an atypical psychedelic; some dissociatives can have CNS depressant effects, thereby carrying similar risks as opioids, which can slow breathing or heart rate to levels resulting in death (w
The respiratory system is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies depending on the size of the organism, the environment in which it lives and its evolutionary history. In land animals the respiratory surface is internalized as linings of the lungs. Gas exchange in the lungs occurs in millions of small air sacs called alveoli in mammals and reptiles, but atria in birds; these microscopic air sacs have a rich blood supply, thus bringing the air into close contact with the blood. These air sacs communicate with the external environment via a system of airways, or hollow tubes, of which the largest is the trachea, which branches in the middle of the chest into the two main bronchi; these enter the lungs where they branch into progressively narrower secondary and tertiary bronchi that branch into numerous smaller tubes, the bronchioles. In birds the bronchioles are termed parabronchi.
It is the bronchioles, or parabronchi that open into the microscopic alveoli in mammals and atria in birds. Air has to be pumped from the environment into the alveoli or atria by the process of breathing which involves the muscles of respiration. In most fish, a number of other aquatic animals the respiratory system consists of gills, which are either or external organs, bathed in the watery environment; this water flows over the gills by a variety of passive means. Gas exchange takes place in the gills which consist of thin or flat filaments and lammelae which expose a large surface area of vascularized tissue to the water. Other animals, such as insects, have respiratory systems with simple anatomical features, in amphibians the skin plays a vital role in gas exchange. Plants have respiratory systems but the directionality of gas exchange can be opposite to that in animals; the respiratory system in plants includes anatomical features such as stomata, that are found in various parts of the plant.
In humans and other mammals, the anatomy of a typical respiratory system is the respiratory tract. The tract is divided into a lower respiratory tract; the upper tract includes the nose, nasal cavities, sinuses and the part of the larynx above the vocal folds. The lower tract includes the lower part of the larynx, the trachea, bronchi and the alveoli; the branching airways of the lower tract are described as the respiratory tree or tracheobronchial tree. The intervals between successive branch points along the various branches of "tree" are referred to as branching "generations", of which there are, in the adult human about 23; the earlier generations, consisting of the trachea and the bronchi, as well as the larger bronchioles which act as air conduits, bringing air to the respiratory bronchioles, alveolar ducts and alveoli, where gas exchange takes place. Bronchioles are defined as the small airways lacking any cartilagenous support; the first bronchi to branch from the trachea are the right and left main bronchi.
Second only in diameter to the trachea, these bronchi enter the lungs at each hilum, where they branch into narrower secondary bronchi known as lobar bronchi, these branch into narrower tertiary bronchi known as segmental bronchi. Further divisions of the segmental bronchi are known as 4th order, 5th order, 6th order segmental bronchi, or grouped together as subsegmental bronchi. Compared to the, on average, 23 number of branchings of the respiratory tree in the adult human, the mouse has only about 13 such branchings; the alveoli are the dead end terminals of the "tree", meaning that any air that enters them has to exit via the same route. A system such as this creates dead space, a volume of air that fills the airways after exhalation and is breathed back into the alveoli before environmental air reaches them. At the end of inhalation the airways are filled with environmental air, exhaled without coming in contact with the gas exchanger; the lungs contract during the breathing cycle, drawing air in and out of the lungs.
The volume of air moved in or out of the lungs under normal resting circumstances, volumes moved during maximally forced inhalation and maximally forced exhalation are measured in humans by spirometry. A typical adult human spirogram with the names given to the various excursions in volume the lungs can undergo is illustrated below: Not all the air in the lungs can be expelled during maximally forced exhalation; this is the residual volume of about 1.0-1.5 liters. Volumes that include the residual volume can therefore not be measured by spirometry, their measurement requires special techniques. The rates at which air is breathed in or out, either through the mouth or nose, or into or out of the alveoli are tabulated below, together with how they are calculated; the number of breath cycles per minute is known as the respiratory rate. In mammals, inhalation at rest is due to the contraction of the diaphragm; this is an upwardly domed sheet of muscle that separates the thoracic cavity from the abdominal cavity.
When it contracts the sheet flattens. The contracting diaphragm pushes, but because the pelvic floo
Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the 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 been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open 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 considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of 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; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is 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, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.
AL-LAD known as 6-allyl-6-nor-LSD, is a psychedelic drug and an analog of lysergic acid diethylamide. It is described by Alexander Shulgin in the book TiHKAL, it is synthesized using allyl bromide as a reactant. While AL-LAD has subtly different effects than LSD, appears to be shorter lasting, their potencies are similar. AL-LAD has a known but short and uncommon history of recreational human use, which originated in Ireland and the UK, but spread internationally. AL-LAD does not cause a color change with the Marquis, Mecke or Mandelin reagents, but does cause the Ehrlich's reagent to turn purple because of the presence of the indole moiety in its structure. AL-LAD is not scheduled by the United Nations' Convention on Psychotropic Substances. AL-LAD is illegal in Denmark. AL-LAD is illegal in Latvia. Although it isn't scheduled, it may be controlled as an LSD structural analog due to an amendment made on June 1, 2015. Romania AL-LAD is illegal in Romania, it is not included directly in the list of controlled substances, but it is included in an analogue act The Riksdag added AL-LAD to Narcotic Drugs Punishments Act under swedish schedule I as of January 26, 2016, published by Medical Products Agency in regulation HSLF-FS 2015:35 listed as 6-allyl-6-nor-LSD, AL-LAD, 6-allyl-N,N-dietyl-9,10-didehydroergolin-8-karboxamid.
AL-LAD is illegal in Switzerland. AL-LAD is illegal in the UK. On June 10, 2014 the UK Advisory Council on the Misuse of Drugs recommended that AL-LAD be named in the UK Misuse of Drugs Act as a class A drug despite not identifying any harm associated with its use; the UK Home office accepted this advice and announced a ban of the substance to be enacted on 6 January 2015 as part of The Misuse of Drugs Act 1971 Order 2014. AL-LAD is not scheduled as a controlled substance at the federal level in the United States, but AL-LAD could be considered an analog of LSD, in which case, sales or possession with intent for human consumption could be prosecuted under the Federal Analogue Act. 1P-LSD ETH-LAD PRO-LAD LSZ Watts, V. J.. E.. "LSD and structural analogs: Pharmacological evaluation at D1 dopamine receptors". Psychopharmacology. 118: 401–9. Doi:10.1007/BF02245940. PMID 7568626. Niwaguchi, T. "Studies on lysergic acid diethylamide and related compounds. IV. Syntheses of various amide derivatives of norlysergic acid and related compounds".
Yakugaku Zasshi. 96: 673–8. Doi:10.1248/yakushi1947.96.5_673. PMID 987200. Robert C. Pfaff, Xuemei Huang, Danuta Marona-Lewicka, Robert Oberlender and David E. Nichols: Lysergamides Revisited. In: NIDA Research Monograph 146: Hallucinogens: An Update. P. 52, 1994, United States Department of Health and Human Services. AL-LAD entry in TiHKAL AL-LAD entry in TiHKAL • info AL-LAD Thread at UKChemicalResearch.org