TCB-2

TCB-2
Clinical data
Routes of; administration	Oral
ATC code	none;
Legal status
Legal status	In General Unscheduled;
Identifiers
	IUPAC name [(7R)-3-Bromo-2,5-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methanamine;
CAS Number	912440-88-1 ; 912342-36-0 (hydrobromide);
PubChem CID	16086382;
ChemSpider	17245036;
UNII	8U6Z2MP6H7;
ChEMBL	ChEMBL379637;
CompTox Dashboard (EPA)	DTXSID201027451 ;
Chemical and physical data
Formula	C11H14BrNO2
Molar mass	272.142 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES COc1c(Br)cc(OC)c2c1CC2CN;
	InChI InChI=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; Key:MPBCKKVERDTCEL-LURJTMIESA-N;
	(verify)

TCB-2 is a hallucinogen discovered in 2006 by Thomas McLean working in the lab of David Nichols at Purdue University.^[1] 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 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.^[1] 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.^[2]

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.^[3]^[4]^[5]^[6] It has also been found to produce rapid antidepressant-, anti-anhedonic-, and anxiolytic-like effects in animals.^[7]

References

^ ^a ^b McLean TH, Parrish JC, Braden MR, Marona-Lewicka D, Gallardo-Godoy A, Nichols DE (September 2006). "1-Aminomethylbenzocycloalkanes: conformationally restricted hallucinogenic phenethylamine analogues as functionally selective 5-HT2A receptor agonists". Journal of Medicinal Chemistry. 49 (19): 5794–803. CiteSeerX 10.1.1.688.9849. doi:10.1021/jm060656o. PMID 16970404.
^ Chang CW, Poteet E, Schetz JA, Gümüş ZH, Weinstein H (2009). "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". Neuropharmacology. 56 (Suppl 1): 213–25. doi:10.1016/j.neuropharm.2008.07.049. PMC 2635340. PMID 18762202.
^ Fox MA, French HT, LaPorte JL, Blackler AR, Murphy DL (September 2010). "The serotonin 5-HT(2A) receptor agonist TCB-2: a behavioral and neurophysiological analysis". Psychopharmacology. 212 (1): 13–23. doi:10.1007/s00213-009-1694-1. PMID 19823806. S2CID 22499760.
^ Aira Z, Buesa I, Salgueiro M, Bilbao J, Aguilera L, Zimmermann M, Azkue JJ (July 2010). "Subtype-specific changes in 5-HT receptor-mediated modulation of C fibre-evoked spinal field potentials are triggered by peripheral nerve injury". Neuroscience. 168 (3): 831–41. doi:10.1016/j.neuroscience.2010.04.032. PMID 20412834. S2CID 207248287.
^ Katsidoni V, Apazoglou K, Panagis G (February 2011). "Role of serotonin 5-HT2A and 5-HT2C receptors on brain stimulation reward and the reward-facilitating effect of cocaine". Psychopharmacology. 213 (2–3): 337–54. doi:10.1007/s00213-010-1887-7. PMID 20577718. S2CID 1580337.
^ Zhang G, Ásgeirsdóttir HN, Cohen SJ, Munchow AH, Barrera MP, Stackman RW (January 2013). "Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice". Neuropharmacology. 64 (1): 403–13. doi:10.1016/j.neuropharm.2012.06.007. PMC 3477617. PMID 22722027.
^ Koike H, Horinokita I, Suzuki M, Futamura T (December 2022). "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". Neuropsychopharmacology. 47 (Suppl 1): 220–370 (270–271). doi:10.1038/s41386-022-01485-0. PMC 9714399. PMID 36456694.

[McLean-1] McLean TH, Parrish JC, Braden MR, Marona-Lewicka D, Gallardo-Godoy A, Nichols DE (September 2006). "1-Aminomethylbenzocycloalkanes: conformationally restricted hallucinogenic phenethylamine analogues as functionally selective 5-HT2A receptor agonists". Journal of Medicinal Chemistry. 49 (19): 5794–803. CiteSeerX 10.1.1.688.9849. doi:10.1021/jm060656o. PMID 16970404.

[2] Chang CW, Poteet E, Schetz JA, Gümüş ZH, Weinstein H (2009). "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". Neuropharmacology. 56 (Suppl 1): 213–25. doi:10.1016/j.neuropharm.2008.07.049. PMC 2635340. PMID 18762202.

[3] Fox MA, French HT, LaPorte JL, Blackler AR, Murphy DL (September 2010). "The serotonin 5-HT(2A) receptor agonist TCB-2: a behavioral and neurophysiological analysis". Psychopharmacology. 212 (1): 13–23. doi:10.1007/s00213-009-1694-1. PMID 19823806. S2CID 22499760.

[4] Aira Z, Buesa I, Salgueiro M, Bilbao J, Aguilera L, Zimmermann M, Azkue JJ (July 2010). "Subtype-specific changes in 5-HT receptor-mediated modulation of C fibre-evoked spinal field potentials are triggered by peripheral nerve injury". Neuroscience. 168 (3): 831–41. doi:10.1016/j.neuroscience.2010.04.032. PMID 20412834. S2CID 207248287.

[5] Katsidoni V, Apazoglou K, Panagis G (February 2011). "Role of serotonin 5-HT2A and 5-HT2C receptors on brain stimulation reward and the reward-facilitating effect of cocaine". Psychopharmacology. 213 (2–3): 337–54. doi:10.1007/s00213-010-1887-7. PMID 20577718. S2CID 1580337.

[6] Zhang G, Ásgeirsdóttir HN, Cohen SJ, Munchow AH, Barrera MP, Stackman RW (January 2013). "Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice". Neuropharmacology. 64 (1): 403–13. doi:10.1016/j.neuropharm.2012.06.007. PMC 3477617. PMID 22722027.

[KoikeHorinokitaSuzuki2022-7] Koike H, Horinokita I, Suzuki M, Futamura T (December 2022). "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". Neuropsychopharmacology. 47 (Suppl 1): 220–370 (270–271). doi:10.1038/s41386-022-01485-0. PMC 9714399. PMID 36456694.

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v t e Phenethylamines
Phenethylamines	Psychedelics: 25B-NBOMe 25C-NBOMe 25D-NBOMe 25I-NBOMe 25N-NBOMe 2C-B 2C-B-AN 2C-Bn 2C-Bu 2C-C 2C-CN 2C-CP 2C-D 2C-E 2C-EF 2C-F 2C-G 2C-G-1 2C-G-2 2C-G-3 2C-G-4 2C-G-5 2C-G-6 2C-G-N 2C-H 2C-I 2C-iP 2C-N 2C-NH2 2C-O 2C-O-4 2C-P 2C-Ph 2C-SE 2C-T 2C-T-2 2C-T-3 2C-T-4 2C-T-5 2C-T-6 2C-T-7 2C-T-8 2C-T-9 2C-T-10 2C-T-11 2C-T-12 2C-T-13 2C-T-14 2C-T-15 2C-T-16 2C-T-17 2C-T-18 2C-T-19 2C-T-20 2C-T-21 2C-T-22 2C-T-22.5 2C-T-23 2C-T-24 2C-T-25 2C-T-27 2C-T-28 2C-T-30 2C-T-31 2C-T-32 2C-T-33 2C-TFE 2C-TFM 2C-YN 2C-V Allylescaline DESOXY Escaline Isoproscaline Jimscaline Macromerine MEPEA Mescaline Metaescaline Methallylescaline Proscaline Psi-2C-T-4 TCB-2 Stimulants: Phenylethanolamine Hordenine Phenethylamine Phenpromethamine α-Methylphenethylamine (amphetamine) β-Methylphenethylamine m-Methylphenethylamine N-Methylphenethylamine o-Methylphenethylamine p-Methylphenethylamine Methylphenidate Entactogens: Lophophine MDPEA MDMPEA Others: BOH DMPEA
Amphetamines	Psychedelics: 3C-AL 3C-BZ 3C-E 3C-MAL 3C-P Aleph Beatrice Bromo-DragonFLY D-Deprenyl DMA DMCPA DMMDA DOB DOC DOEF DOET DOI DOM DON DOPR DOTFM Ganesha MMDA MMDA-2 Psi-DOM TMA TeMA ZDCM-04 Stimulants: 2-FA 2-FMA 3-FA 3-FMA Acridorex Alfetamine Amfecloral Amfepentorex Amphetamine (Dextroamphetamine, Levoamphetamine) Amphetaminil Benfluorex Benzphetamine Cathine Clobenzorex Dimethylamphetamine Ephedrine Etilamfetamine Fencamfamin Fencamine Fenethylline Fenfluramine (Dexfenfluramine, Levofenfluramine) Fenproporex Flucetorex Fludorex Formetorex Furfenorex Gepefrine 4-Hydroxyamphetamine Iofetamine Isopropylamphetamine Lefetamine Lisdexamfetamine Mefenorex Metaraminol Methamphetamine (Dextromethamphetamine, Levomethamphetamine) Methoxyphenamine MMA Morforex Norfenfluramine L-Norpseudoephedrine N,alpha-Diethylphenylethylamine Oxifentorex Oxilofrine Ortetamine PBA PCA PFA PFMA PIA PMA PMEA PMMA Phenylpropanolamine Pholedrine Prenylamine Propylamphetamine Pseudoephedrine Sibutramine Tiflorex Tranylcypromine Xylopropamine Zylofuramine Entactogens: 4-FA 4-FMA 4-MA 4-MMA 4-MTA 5-APB 5-APDB 5-EAPB 5-IT 5-MAPB 5-MAPDB 6-APB 6-APDB 6-Chloro-MDMA 6-EAPB 6-IT 6-MAPB 6-MAPDB EDA IAP 2,3-MDA 3,4-MDA (tenamfetamine) MDEA MDHMA MDMA (midomafetamine) MDOH Methamnetamine MMDMA Naphthylaminopropane TAP Others: 3,4-DCA Amiflamine DiFMDA Selegiline (also D-Deprenyl)
Phentermines	Stimulants: Chlorphentermine Cloforex Clortermine Etolorex Mephentermine Pentorex Phentermine Entactogens: MDPH MDMPH Others: Cericlamine
Cathinones	Stimulants: 3-FMC 4-MC 4-BMC 4-CMC 4-EMC 4-FMC 4-MEC 4-MeMABP 4-MPD Amfepramone Benzedrone Brephedrone Buphedrone Bupropion Cathinone Dimethylcathinone Ethcathinone Eutylone Hydroxybupropion Methcathinone Methedrone NEB N-Ethylhexedrone N-Ethylpentedrone Pentedrone Pentylone Radafaxine Entactogens: 3,4-DMMC 3-MMC Butylone Ethylone Methylone Methylenedioxycathinone Mephedrone
Phenylisobutylamines	Entactogens: 4-CAB 4-MAB Ariadne BDB Butylone EBDB Eutylone MBDB Stimulants: Phenylisobutylamine
Phenylalkylpyrrolidines	Stimulants: α-PBP α-PHP α-PPP α-PVP MDPBP MDPPP MDPV 4-MePBP 4-MePHP 4-MePPP MOPPP MOPVP MPBP MPHP MPPP Naphyrone PEP Prolintane Pyrovalerone
Catecholamines (and close relatives)	6-FNE 6-OHDA a-Me-DA a-Me-TRA Adrenochrome Ciladopa D-DOPA (Dextrodopa) Dimetofrine Dopamine Epinephrine Epinine Etilefrine Ethylnorepinephrine Fenclonine Ibopamine Isoprenaline Isoetarine L-DOPA (Levodopa) L-DOPS (Droxidopa) L-Phenylalanine L-Tyrosine m-Tyramine Metanephrine Metaraminol Metaterol Metirosine Methyldopa N,N-Dimethyldopamine Nordefrin (Levonordefrin) Norepinephrine Norfenefrine (m-Octopamine) Normetanephrine Orciprenaline p-Octopamine p-Tyramine Phenylephrine Synephrine
Miscellaneous	AL-LAD Amidephrine Arbutamine Cafedrine Denopamine Desvenlafaxine Diphenidine Dizocilpine Dobutamine Dopexamine Ephenidine Etafedrine ETH-LAD Famprofazone Fluorolintane Hexapradol IP-LAD Lysergic acid amide Lysergic acid 2-butyl amide Lysergic acid 2,4-dimethylazetidide Lysergic acid diethylamide Methoxamine Methoxphenidine MT-45 PARGY-LAD Phenibut PRO-LAD Pronethalol Salbutamol (Levosalbutamol) Solriamfetol Theodrenaline Thiamphenicol UWA-101 Venlafaxine

See also

References