Serotonin receptor agonists

A serotonin receptor agonist is a compound that activates serotonin receptors, in a manner similar to serotonin.  It includes a large number of legal drugs and an equally large number of illegal drugs.  The class also includes a very large number of pharmaceuticals that found their way to clinical trial, were rejected, were resubmitted for something else, were rejected and so it goes on.  The following is not atypical

“EMD-49,980 is a dopaminergic and serotonergic drug which was originally developed for the treatment of schizophrenia. In clinical trials its antipsychotic efficacy was only modest but it was unexpectedly found to produce antidepressant and anxiolytic effects. As a result, it was further researched for the treatment of depression instead. It has also been investigated as a therapy for Parkinson's disease and prolactinoma” [source Wikipedia]

A few of the drugs that never make it go onto the recreational market to recoup the losses made in investigation.  This is a somewhat worrying trend as many are rejected because of severe reactions – such as hepatoxicity. 

Universities appear to be a primary area for experimentation in new drugs.  They call them ‘novel’, but new will do. 

Purdue University in the USA, for example, appear to have an almost unlimited budget to make and then release new drugs on the market.  Professor Nichols, Chair in Pharmacology at Purdue University has invented well over 250 drugs including TFMFly , BromoDragonFLY, DMBMPP, escaline, LSZ, 6-APB, 2C-I-NBOMe, 2CBCB-NBOMe , 25I-NBMD and other NBOMe variants, several LSD analogues, including ETH-LAD, PRO-LAD, and AL-LAD, all more potent than LSD itself; MDA, 5-methyl-MDA, 4-MTA and MDAI.  A number of compounds included in Shulgin's PIHKAL were actually first synthesized in Nichols's lab. He also ‘improved the synthesis of psilocybin’.  TCB-2 is a hallucinogen, discovered in 2006 by Thomas McLean, working in the lab of Prof. David Nichols at Purdue University where it was named 2C-BCB.  There are so many we have not listed them all below.   None of these drugs has any medicinal value.

25I-NBOH; 25I-NBOMe, 25TFM-NBOMe, 2CBFly-NBOMe and 25B-NBOMe were invented in 2003 by Ralf Heim at the Free University of Berlin, but were subsequently investigated by a team at Purdue University .  25CN-NBOH was invented in 2011 by Martin Hansen at the University of Copenhagen.

Overall we can conclude that it is universities from which all these new [illegal or street] drugs derive if the evidence is anything to go by.

ILLEGAL

5-MeO-DMT – agonist for 5HT1A, 5HT2A, 5HT2C

Cannabis – agonist for  5HT1A; Cannabidiol (CBD), for example is one of at least 85 active cannabinoids identified in cannabis

Psilocin – agonist for  5HT1A, 5HT2A, 5HT2B, 5HT2C

Mescaline – agonist for 5HT2A, 5HT2C

Psilocybin – agonist for  5HT1A, 5HT2A, 5HT2B, 5HT2C

2C-B - agonist for  5HT2A, 5HT2C

2C family – see link for more details

DO family – see link for more details

LSD - agonist for  5HT1A, 5HT1D, 5HT2A, 5HT2C, 5HT5A, 5HT6, 5HT7

Bromo-DragonFLY - 5HT2A

DMT – agonist for  5HT1A, 5HT1B, 5HT1D, 5HT2A, 5HT2B, 5HT2C

MDxx family - e.g., MDA, MDMA, MDOH, MMDA

Other Miscellaneous ‘recreational’ drugs – eg.  Dimemebfe, mCPP, ‘Legal X’ [including TFMPP and BZP]

LEGAL

Amphetamines - agonist for  5HT1A, 5HT2B
eg. chlorphentermine, cloforex, dexfenfluramine, fenfluramine, levofenfluramine, norfenfluramine

Alcohols – agonist for  5HT3,
e.g., butanol, ethanol, trichloroethanol

Anti-depressants - e.g., etoperidone, nefazodone, trazodone, vilazodone, vortioxetine; Oxaflozane; Vilazodone;  (brand name Conflictan ; and research chemicals such as Osemozotan

Anti-emetics – such as Renzapride

Atypical antipsychotics  - e.g., aripiprazole, asenapine, clozapine, lurasidone, quetiapine, ziprasidone; Vortioxetine (trade name Brintellix); and  Antipsychotics such as Buspirone

Anti-anxiety drugs – such as the Azapirones e.g., buspirone, eptapirone, gepirone, perospirone, tandospirone; Oxaflozane (brand name Conflictan); Tandospirone (Sediel);and research chemicals such as Osemozotan

Antivirals – such as Efavirenz

Pain killers and NSAIDs – such as Befiradol; and research chemicals such as Osemozotan which has analgesic effects in animal studies

Dopamine – 5HT1A,

‘Serenic’ and anti-aggression drugs – only one in this class Eltoprazine which is an agonist at the 5-HT1A and 5-HT1B receptors and an antagonist at the 5-HT2C receptor; there is also a research chemical -  Osemozotan which has ‘antiobsessional’ and  serenic activity in animal studies

Migraine and cluster headache attack drugs –  including the Ergolines e.g., bromocriptine, cabergoline, dihydroergotamine, ergotamine, lisuride, methylergometrine (methylergonovine), methysergide, pergolide; the Triptans e.g., avitriptan, donitriptan, eletriptan, sumatriptan, zolmitriptan; Metoclopramide

Vasoconstrictors – agonist for  5HT1 receptors; including the ergolines [see above]; and alpha blockers such as Urapidil

FSIAD/HSDD drugs – for example Flibanserin

Volatiles/gases  - agonist for 5HT3
e.g., halothane, isoflurane, toluene, trichloroethane

IBS and gastro-intestinal disease drugs – such as Tegaserod is a 5-HT4 agonist sold under the names Zelnorm and Zelmac for the management of irritable bowel syndrome and constipation; and Prucalopride (brand names Resolor, and Resotran); Mosapride; Metoclopramide; Cisapride (trade names Prepulsid and Propulsid); Cinitapride (Cintapro, Pemix)

‘Anorectic weight-loss’ or obesity drugs – such as Loraserin.  Some drugs in this group have already been withdrawn from the market because they are implicated in cardiac fibrosis eg Fenfluramine.  

Parkinson’s disease treatments like Pergolide

Serotonin – agonist for 5HT1A, 5HT1B, 5HT1D, 5HT1E, 5HT1F, 5HT2A, 5HT2B, 5HT2C, 5HT3, 5HT4, 5HT5A, 5HT6, 5HT7

Observations

For iPad/iPhone users: tap letter twice to get list of items.

• Long-term lithium treatment causes serotonin receptor down-regulation via serotonergic presynapses in rat brain
• Methylphenidate intoxication: somnolence as an uncommon clinical symptom and proof of overdosing by increased serum levels of ritalinic acid
• Severe clinical toxicity associated with analytically confirmed recreational use of 25I-NBOMe: case series
• There Was Life In Those Eyes MMDA by Morninggloryseed