TCB-2

{{Short description|Potent hallucinogenic drug discovered in 2006}}

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{{Drugbox

| verifiedrevid = 448096412

| IUPAC_name = [(7R)-3-Bromo-2,5-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methanamine

| image = TCB-2.png

| width =

| tradename =

| pregnancy_category =

| legal_status = In General Unscheduled

| routes_of_administration = Oral

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 912440-88-1

| CAS_supplemental =
912342-36-0 (hydrobromide)

| ATC_prefix = none

| ATC_suffix =

| PubChem = 16086382

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank =

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 8U6Z2MP6H7

| ChemSpiderID = 17245036

| ChEMBL = 379637

| synonyms =

| C=11 | H=14 | Br=1 | N=1 | O=2

| SMILES = COc1c(Br)cc(OC)c2c1CC2CN

| StdInChI = 1S/C11H14BrNO2/c1-14-9-4-8(12)11(15-2)7-3-6(5-13)10(7)9/h4,6H,3,5,13H2,1-2H3/t6-/m0/s1

| StdInChIKey = MPBCKKVERDTCEL-LURJTMIESA-N

}}

TCB-2 is a hallucinogen discovered in 2006 by Thomas McLean working in the lab of David Nichols at Purdue University.{{cite journal | vauthors = McLean TH, Parrish JC, Braden MR, Marona-Lewicka D, Gallardo-Godoy A, Nichols DE | title = 1-Aminomethylbenzocycloalkanes: conformationally restricted hallucinogenic phenethylamine analogues as functionally selective 5-HT2A receptor agonists | journal = Journal of Medicinal Chemistry | volume = 49 | issue = 19 | pages = 5794–803 | date = September 2006 | pmid = 16970404 | doi = 10.1021/jm060656o | citeseerx = 10.1.1.688.9849 }} It is a conformationally-restricted derivative of the phenethylamine 2C-B, also a hallucinogen, and acts as a potent agonist for the 5-HT_2A and 5-HT_2C receptors with a K_i of 0.26{{nbsp}}nM at the human 5-HT_2A 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-HT_2A receptor-mediated responses from those produced by other similar receptors.{{cite journal | vauthors = Chang CW, Poteet E, Schetz JA, Gümüş ZH, Weinstein H | title = Towards a quantitative representation of the cell signaling mechanisms of hallucinogens: measurement and mathematical modeling of 5-HT1A and 5-HT2A receptor-mediated ERK1/2 activation | journal = Neuropharmacology | volume = 56 | pages = 213–25 | year = 2009 | issue = Suppl 1 | pmid = 18762202 | pmc = 2635340 | doi = 10.1016/j.neuropharm.2008.07.049 }}

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-HT_2A receptor differs from that of other serotonin receptors in a number of animal models, such as studies of cocaine addiction and neuropathic pain.{{cite journal | vauthors = Fox MA, French HT, LaPorte JL, Blackler AR, Murphy DL | title = The serotonin 5-HT(2A) receptor agonist TCB-2: a behavioral and neurophysiological analysis | journal = Psychopharmacology | volume = 212 | issue = 1 | pages = 13–23 | date = September 2010 | pmid = 19823806 | doi = 10.1007/s00213-009-1694-1 | s2cid = 22499760 }}{{cite journal | vauthors = Aira Z, Buesa I, Salgueiro M, Bilbao J, Aguilera L, Zimmermann M, Azkue JJ | title = Subtype-specific changes in 5-HT receptor-mediated modulation of C fibre-evoked spinal field potentials are triggered by peripheral nerve injury | journal = Neuroscience | volume = 168 | issue = 3 | pages = 831–41 | date = July 2010 | pmid = 20412834 | doi = 10.1016/j.neuroscience.2010.04.032 | s2cid = 207248287 }}{{cite journal | vauthors = Katsidoni V, Apazoglou K, Panagis G | title = Role of serotonin 5-HT2A and 5-HT2C receptors on brain stimulation reward and the reward-facilitating effect of cocaine | journal = Psychopharmacology | volume = 213 | issue = 2–3 | pages = 337–54 | date = February 2011 | pmid = 20577718 | doi = 10.1007/s00213-010-1887-7 | s2cid = 1580337 }}{{cite journal | vauthors = Zhang G, Ásgeirsdóttir HN, Cohen SJ, Munchow AH, Barrera MP, Stackman RW | title = Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice | journal = Neuropharmacology | volume = 64 | pages = 403–13 | date = January 2013 | issue = 1 | pmid = 22722027 | pmc = 3477617 | doi = 10.1016/j.neuropharm.2012.06.007 }} It has also been found to produce rapid antidepressant-, anti-anhedonic-, and anxiolytic-like effects in animals.{{cite journal | vauthors = Koike H, Horinokita I, Suzuki M, Futamura T | title = ACNP 61st Annual Meeting: Poster Abstracts P271-P540: P360. A Potent 5-HT2A Receptor Agonist TCB-2 Exerts Rapid Antidepressant-Like and Anxiolytic-Like Effects in Mice | journal = Neuropsychopharmacology | volume = 47 | issue = Suppl 1 | pages = 220–370 (270–271) | date = December 2022 | pmid = 36456694 | pmc = 9714399 | doi = 10.1038/s41386-022-01485-0 | url = }}