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.
The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations.
Etoperidone, associated with several brand names, is an atypical antidepressant which was developed in the 1970s and either is no longer marketed or was never marketed. It is a phenylpiperazine related to trazodone and nefazodone in chemical structure and is a serotonin antagonist and reuptake inhibitor (SARI) similarly to them.
Tandospirone, sold under the brand name Sediel, is an anxiolytic and antidepressant medication used in Japan and China, where it is marketed by Dainippon Sumitomo Pharma. It is a member of the azapirone class of drugs and is closely related to other azapirones like buspirone and gepirone.
Mesulergine (INNTooltip International Nonproprietary Name) (developmental code name CU-32085) is a drug of the ergoline group which was never marketed. It acts on serotonin and dopamine receptors. Specifically, it is an agonist of dopamine D2-like receptors and serotonin 5-HT6 receptors and an antagonist of serotonin 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT7 receptors. It also has affinity for the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, and 5-HT5A receptors. The compound had entered clinical trials for the treatment of Parkinson's disease; however, further development was halted due to adverse histological abnormalities in rats. It was also investigated for the treatment of hyperprolactinemia (high prolactin levels).
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.
YM-348 is an indazole derivative drug which acts as a potent and selective 5-HT2C receptor agonist, with an EC50 of 1nM and 15x selectivity over 5-HT2A, although it only has moderate selectivity of 3x over the closely related 5-HT2B receptor. It has thermogenic and anorectic effects in animal studies, making it potentially useful for the treatment of obesity.
PNU-22394 is a drug which acts as an agonist at serotonin 5-HT2 receptors, with strongest binding affinity for 5-HT2A and 5-HT2C and slightly weaker at 5-HT2B, although it is only a full agonist at 5-HT2C, but partial agonist at 5-HT2A and 5-HT2B. It has anorectic effects in both animal studies and human trials, along with "Pro-Cognitive Properties", although it has never been developed for medical use.
Oxaflozane (INN) (brand name Conflictan) is an antidepressant and anxiolytic drug that was introduced by Solvay in France in 1982 for the treatment of depression but has since been discontinued. It is a prodrug of flumexadol (N-dealkyloxaflozane; 2-(3-trifluoromethylphenyl)morpholine; CERM-1841 or 1841-CERM), which is reported to act as an agonist of the serotonin 5-HT1A (pKi = 7.1) and 5-HT2C (pKi = 7.5) receptors and, to a much lesser extent, of the 5-HT2A (pKi = 6.0) receptor. In addition to its serotonergic properties, oxaflozane may also produce anticholinergic side effects at high doses, namely in overdose.
Serotonin antagonist and reuptake inhibitors (SARIs) are a class of drugs used mainly as antidepressants, but also as anxiolytics and hypnotics. They act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of serotonin, norepinephrine, and/or dopamine. Additionally, most also antagonize α1-adrenergic receptors. The majority of the currently marketed SARIs belong to the phenylpiperazine class of compounds.
Vabicaserin was a novel antipsychotic and anorectic under development by Wyeth. As of 2010 it is no longer in clinical trials for the treatment of psychosis. It was also under investigation as an antidepressant but this indication appears to have been dropped as well.
Adatanserin is a mixed 5-HT1A receptor partial agonist and 5-HT2A and 5-HT2C receptor antagonist. It was under development by Wyeth as an antidepressant but was ultimately not pursued.
G-130 is a drug with stimulant and anorectic effects, related to phenmetrazine.
5-MeO-NBpBrT is a N-substituted member of the methoxytryptamine family of compounds. Like other such compounds it acts as an antagonist for the 5-HT2A receptor, with a claimed 100x selectivity over the closely related 5-HT2C receptor. While N-benzyl substitution of psychedelic phenethylamines often results in potent 5-HT2A agonists, it had been thought that N-benzyl tryptamines show much lower efficacy and are either very weak partial agonists or antagonists at 5-HT2A, though more recent research has shown stronger agonist activity for 3-substituted benzyl derivatives. Extending the benzyl group to a substituted phenethyl can also recover agonist activity in certain cases.
5-HT2C receptor agonists are a class of drugs that activate 5-HT2C receptors. They have been investigated for the treatment of a number of conditions including obesity, psychiatric disorders, sexual dysfunction and urinary incontinence.
PNU-181731 is a drug which acts as an agonist at serotonin 5-HT2 receptors, with strongest binding affinity for the 5-HT2C subtype at 4.8nM, and weaker 5-HT2A affinity of 18nM. It has anxiolytic effects in animal studies with around one tenth the potency of alprazolam and no significant ataxia or other side effects noted.
PHA-57378 is a drug which acts as an agonist at serotonin 5-HT2 receptors, having a binding affinity of 4.1 nM at the 5-HT2A subtype and 4.3 nM at 5-HT2C. It has anxiolytic effects in animal studies.
25CN-NBOH is a compound indirectly derived from the phenethylamine series of hallucinogens, which was discovered in 2014 at the University of Copenhagen. This compound is notable as one of the most selective agonist ligands for the 5-HT2A receptor yet discovered, with a pKi of 8.88 at the human 5-HT2A receptor and with 100x selectivity for 5-HT2A over 5-HT2C, and 46x selectivity for 5-HT2A over 5-HT2B. A tritiated version of 25CN-NBOH has also been accessed and used for more detailed investigations of the binding to 5-HT2 receptors and autoradiography.
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.
