Psilocin is a substituted tryptamine alkaloid and a serotonergic psychedelic substance. It is present in most psychedelic mushrooms together with its phosphorylated counterpart psilocybin. Psilocin is a Schedule I drug under the Convention on Psychotropic Substances. Acting on the 5-HT2A receptors, psilocin modulates the production and reuptake of serotonin. The mind-altering effects of psilocin are highly variable and subjective and resemble those of LSD and DMT.
2C-TFM is a psychedelic phenethylamine of the 2C family. It was first synthesized in the laboratory of David E. Nichols. It has also been called 2C-CF3, a name derived from the Para-trifluoromethyl group it contains.
2C-B-FLY is a psychedelic phenethylamine and designer drug of the 2C family. It was first synthesized in 1996 by Aaron Monte, Professor of Chemistry at UW-La Crosse.
A serotonin receptor agonist is an agonist of one or more serotonin receptors. They activate serotonin receptors in a manner similar to that of serotonin, a neurotransmitter and hormone and the endogenous ligand of the serotonin receptors.
TCB-2 is a hallucinogen discovered in 2006 by Thomas McLean working in the lab of David Nichols at Purdue University. It is a conformationally-restricted derivative of the phenethylamine 2C-B, also a hallucinogen, and acts as a potent agonist for the 5-HT2A and 5-HT2C receptors with a Ki of 0.26 nM at the human 5-HT2A receptor. In drug-substitution experiments in rats, TCB-2 was found to be of similar potency to both LSD and Bromo-DragonFLY, ranking it among the most potent phenethylamine hallucinogens yet discovered. This high potency and selectivity has made TCB-2 useful for distinguishing 5-HT2A mediated responses from those produced by other similar receptors. TCB-2 has similar but not identical effects in animals to related phenethylamine hallucinogens such as DOI, and has been used for studying how the function of the 5-HT2A receptor differs from that of other serotonin receptors in a number of animal models, such as studies of cocaine addiction and neuropathic pain.
2,5-Dimethoxy-4-trifluoromethylamphetamine (DOTFM) is a psychedelic drug of the phenethylamine and amphetamine chemical classes. It was first synthesized in 1994 by a team at Purdue University led by David E. Nichols. DOTFM is the alpha-methylated analogue of 2C-TFM, and is around twice as potent in animal studies. It acts as an agonist at the 5-HT2A and 5-HT2C receptors. In drug-substitution experiments in rats, DOTFM fully substituted for LSD and was slightly more potent than DOI.
4-HO-MPMI (also known as 4-Hydroxy-N-methyl-(α,N-trimethylene)-tryptamine or lucigenol) is a tryptamine derivative that is a psychedelic drug. It was developed by the team led by David Nichols from Purdue University in the late 1990s. This compound produces hallucinogen-appropriate responding in animal tests with a similar potency to the amphetamine-derived psychedelic DOI, and has two enantiomers, with only the (R)-enantiomer being active.
5-MeO-MPMI (also known as 5-Methoxy-N-methyl-(α,N-trimethylene)tryptamine) is a tryptamine derivative that is a psychedelic drug. It was first developed by the team led by JE Macor in 1992, and subsequently investigated by the team led by David Nichols from Purdue University in the late 1990s. This compound produces psychedelic-appropriate responding in animal tests with a similar potency to the amphetamine-derived psychedelic DOI, and has two enantiomers, with only the (R)-enantiomer being active.
Lysergic acid 2,4-dimethylazetidide (LA-SS-Az, LSZ) is an analog of LSD developed by the team led by David E. Nichols at Purdue University. It was developed as a rigid analog of LSD with the diethylamide group constrained into an azetidine ring in order to map the binding site at the 5-HT2A receptor. There are three possible stereoisomers around the azetidine ring, with the (S,S)-(+) isomer being the most active, slightly more potent than LSD itself in drug discrimination tests using trained rats.
Lysergic acid 2-butyl amide (2-Butyllysergamide, LSB) is an analogue of LSD originally developed by Richard Pioch at Eli Lilly in the 1950s, but mostly publicised through research conducted by the team led by David E. Nichols at Purdue University. It is a structural isomer of LSD, with the two ethyl groups on the amide nitrogen having been replaced by a single sec-butyl group, joined at the 2-position. It is one of the few lysergamide derivatives to exceed the potency of LSD in animal drug discrimination assays, with the (R) isomer having an ED50 of 33nmol/kg for producing drug-appropriate responding, vs 48nmol/kg for LSD itself. The corresponding (R)-2-pentyl analogue has higher binding affinity for the 5-HT1A and 5-HT2A receptors, but is less potent in producing drug-appropriate responding, suggesting that the butyl compound has a higher efficacy at the receptor target. The drug discrimination assay for LSD in rats involves both 5-HT1A and 5-HT2A mediated components, and while lysergic acid 2-butyl amide is more potent than LSD as a 5-HT1A agonist, it is slightly less potent as a 5-HT2A agonist, and so would probably be slightly less potent than LSD as a hallucinogen in humans. The main use for this drug has been in studies of the binding site at the 5-HT2A receptor through which LSD exerts most of its pharmacological effects, with the stereoselective activity of these unsymmetric monoalkyl lysergamides foreshadowing the subsequent development of compounds such as lysergic acid 2,4-dimethylazetidide (LSZ).
Jimscaline (C-(4,5,6-trimethoxyindan-1-yl)methanamine) is a conformationally-restricted derivative of the cactus-derived hallucinogen mescaline, which was discovered in 2006 by a team at Purdue University led by David E. Nichols. It acts as a potent agonist for the 5-HT2A and 5-HT2C receptors with the more active (R)-enantiomer having a Ki of 69 nM at the human 5-HT2A receptor, and around three times the potency of mescaline in drug-substitution experiments in animals. This discovery that the side chain of the phenethylamine hallucinogens could be constrained to give chiral ligands with increased activity then led to the later development of the super-potent benzocyclobutene derivative TCB-2.
TFMFly is a compound related to psychedelic phenethylamines such as 2C-B-FLY and 2C-TFM. It was first reported in 2005 by a team at Purdue University led by David Nichols. It acts as a potent agonist at the 5HT2A serotonin receptor subtype, and is a chiral compound with the more active (R) enantiomer having a Ki of 0.12 nM at the human 5-HT2A receptor. While the fully aromatic benzodifurans such as Bromo-DragonFLY generally have higher binding affinity than saturated compounds like 2C-B-FLY, the saturated compounds have higher efficacy as agonists.
2,5-Dimethoxy-4-fluoroamphetamine (DOF) is a psychedelic drug of the phenethylamine and amphetamine classes. Alexander Shulgin briefly describes DOF in his book PiHKAL:
Animal studies that have compared DOF to the highly potent DOI and DOB imply that the human activity will be some four to six times less than these two heavier halide analogues.
5-Fluoro-N,N-dimethyltryptamine is a tryptamine derivative related to compounds such as 5-bromo-DMT and 5-MeO-DMT. Fluorination of psychedelic tryptamines either reduces or has little effect on 5-HT2A/C receptor affinity or intrinsic activity, although 6-fluoro-DET is inactive as a psychedelic despite acting as a 5-HT2A agonist, while 4-fluoro-5-methoxy-DMT is a much stronger agonist at 5-HT1A than 5-HT2A.
LY-293284 is a research chemical developed by the pharmaceutical company Eli Lilly and used for scientific studies. It acts as a potent and selective 5-HT1A receptor full agonist. It was derived through structural simplification of the ergoline based psychedelic LSD, but is far more selective for 5-HT1A with over 1000× selectivity over other serotonin receptor subtypes and other targets. It has anxiogenic effects in animal studies.
2CB-Ind is a conformationally-restricted derivative of the phenethylamine hallucinogen 2C-B, discovered in 1974 by Alexander Shulgin. It acts as a moderately potent and selective agonist for the 5-HT2A and 5-HT2C receptors, but unlike the corresponding benzocyclobutene derivative TCB-2 which is considerably more potent than the parent compound 2C-B, 2CB-Ind is several times weaker, with racemic 2CB-Ind having a Ki of 47nM at the human 5-HT2A receptor, only slightly more potent than the mescaline analogue (R)-jimscaline.
DMBMPP, or 2-(2,5-dimethoxy-4-bromobenzyl)-6-(2-methoxyphenyl)piperidine, is a 2-benzylpiperidine analog of the hallucinogenic N-benzylphenethylamine 25B-NBOMe and was discovered in 2011 by Jose Juncosa in the group of David E. Nichols at Purdue University. DMBMPP differs from 25B-NBOMe by incorporating the amine within a piperidine ring, making for a more rigid molecular structure than that of the open-chain 25B-NBOMe. The presence of the piperidine ring introduces two stereocenters, thus, four stereoisomers of this compound can be made.
2C-B-BUTTERFLY is a conformationally-restricted derivative of the phenethylamine hallucinogen 2C-B, which was discovered in 1999 by Michael S. Whiteside and Aaron Monte. It is a ring-expanded homologue of the better known compound 2C-B-FLY, and has similar properties as an agonist for serotonin receptors, but with more selectivity for 5-HT2C over 5-HT2A.
DOB-FLY is a recreational designer drug with psychedelic effects. It can be regarded as the alpha-methyl derivative of 2C-B-FLY or the partially saturated counterpart of bromo-dragonfly. Unlike bromo-dragonfly, DOB-FLY is only slightly more potent than DOB itself, with an active dose in humans of around 1 mg.
6-Fluoro-DET is a substituted tryptamine derivative related to drugs such as DET and 5-fluoro-DET. It acts as a partial agonist at the 5-HT2A receptor, but while it produces similar physiological effects to psychedelic drugs, it does not appear to produce psychedelic effects itself even at high doses. For this reason it saw some use as an active placebo in early clinical trials of psychedelic drugs but was regarded as having little use otherwise, though more recent research into compounds such as AL-34662, TBG and AAZ-A-154 has shown that these kind of non-psychedelic 5-HT2A agonists can have various useful applications.
