1-Ethyl-6-hydroxytryptoline

vanc 6 1-Ethyl-6-hydroxytryptoline.svg skin-invert-image 225px Serotonin 5-HT2 receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonin 5-HT2C receptor agonist None 3071387 2330921 5221228 1-Et-6-OH-THβC; Compound 29 1-ethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-6-ol 13 16 2 1 CCC1C2=C(CCN1)C3=C(N2)C=CC(=C3)O 1S/C13H16N2O/c1-2-11-13-9(5-6-14-11)10-7-8(16)3-4-12(10)15-13/h3-4,7,11,14-16H,2,5-6H2,1H3 JYRSBENZEDBDCG-UHFFFAOYSA-N 1-Ethyl-6-hydroxytryptoline (1-Et-6-OH-THβC) is a serotonin 5-HT2 receptor agonist of the β-carboline family related to tryptoline. Orr MJ, Cao AB, Wang CT, Gaisin A, Csakai A, Friswold AP, Meltzer HY, McCorvy JD, Scheidt KA April 2022 Discovery of Highly Potent Serotonin 5-HT2 Receptor Agonists Inspired by Heteroyohimbine Natural Products ACS Medicinal Chemistry Letters 13 4 648–657 10.1021/acsmedchemlett.1c00694 9014500 35450369 Aliphatic substitution at the 1 position gave rise to active compounds as well (26−29), though only 1-ethyl compound 29 had full agonist activity at both receptors It is the 1-ethyl and 6-hydroxy derivative of tryptoline. The drug has been found to act as a potent agonist of the serotonin 5-HT2A and 5-HT2C receptors, with EC50 half-maximal effective concentration (Emax maximal efficacy) values of 195nM (85%) and 61nM (98%) in terms of Gq-mediated calcium flux, respectively. This is in notable contrast to other β-carbolines like harmine and harmaline, which are inactive as serotonin 5-HT2A receptor agonists. Rabin RA, Regina M, Doat M, Winter JC May 2002 5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens Pharmacology, Biochemistry, and Behavior 72 1–2 29–37 10.1016/s0091-3057(01)00720-1 11900766 Rolquin JD 3 May 2022 Examining Ayahuasca Constituents at 5-HT2A Receptors in Search of Antidepressant Action VCU Scholars Compass https://scholarscompass.vcu.edu/etd/6884/ 7 April 2026 Grella B, Teitler M, Smith C, Herrick-Davis K, Glennon RA December 2003 Binding of beta-carbolines at 5-HT(2) serotonin receptors Bioorganic & Medicinal Chemistry Letters 13 24 4421–4425 10.1016/j.bmcl.2003.09.027 14643338 [...] several β-carbolines, including harmaline (1) and its positional isomer 6-methoxyharmalan (4) substituted for the hallucinogenic (5-HT2A agonist) phenylalkylamine [DOM] in a drug discrimination task with rats trained to discriminate DOM from saline vehicle.10 However, neither harmaline (1; Ki=7790 nM) nor 6-methoxyharmalan (4; Ki=5600 nM) binds with high affinity at 5-HT2A receptors, and both were found to lack action as 5-HT2A agonists in a phosphoinositol (PI) hydrolysis assay.5,9 [...] At this time, it is not known if the actions of 1 and 4 in the PI hydrolysis assay reflect their low affinity, low efficacy, or whether the actions of the β-carbolines (in drug discrimination and/or other assays) is attributable to, or compromised by, their actions at other populations of receptors—particularly 5-HT receptors—or by possible interactions with the serotonin transporter. It is also in apparent contrast to tryptoline, which shows very low affinity for the serotonin 5-HT2A receptor (Ki = 3,900nM) Bojarski AJ, Cegła MT, Charakchieva-Minol S, Mokrosz MJ, Maćkowiak M, Misztal S, Mokrosz JL April 1993 Structure-activity relationship studies of CNS agents. Part 9: 5-HT1A and 5-HT2 receptor affinity of some 2- and 3-substituted 1,2,3,4-tetrahydro-beta-carbolines Die Pharmazie 48 4 289–294 8321880 https://www.researchgate.net/profile/Marek-Cegla-2/publication/14877180_Structure-activity_relationship_studies_of_CNS_agents_Part_9_5-HT1A_and_5-HT2_receptor_affinity_of_some_2-_and_3-substituted_1234-tetrahydro-b-carbolines/links/5538ce710cf2239f4e79ba51/Structure-activity-relationship-studies-of-CNS-agents-Part-9-5-HT1A-and-5-HT2-receptor-affinity-of-some-2-and-3-substituted-1-2-3-4-tetrahydro-b-carbolines.pdf 2026-04-04 2026-04-07 https://web.archive.org/web/20260404220751/https://www.researchgate.net/profile/Marek-Cegla-2/publication/14877180_Structure-activity_relationship_studies_of_CNS_agents_Part_9_5-HT1A_and_5-HT2_receptor_affinity_of_some_2-_and_3-substituted_1234-tetrahydro-b-carbolines/links/5538ce710cf2239f4e79ba51/Structure-activity-relationship-studies-of-CNS-agents-Part-9-5-HT1A-and-5-HT2-receptor-affinity-of-some-2-and-3-substituted-1-2-3-4-tetrahydro-b-carbolines.pdf bot: unknown and is inactive as an agonist of the serotonin 5-HT2B receptor (KB = >3,000nM). Audia JE, Evrard DA, Murdoch GR, Droste JJ, Nissen JS, Schenck KW, Fludzinski P, Lucaites VL, Nelson DL, Cohen ML July 1996 Potent, selective tetrahydro-beta-carboline antagonists of the serotonin 2B (5HT2B) contractile receptor in the rat stomach fundus Journal of Medicinal Chemistry 39 14 2773–2780 10.1021/jm960062t 8709108 The chemical synthesis of 1-ethyl-6-hydroxytryptoline has been described. An analogue, 1-(2,4,5-trimethoxyphenyl)-6-chlorotryptoline, is far more potent as a serotonin 5-HT2A and 5-HT2C receptor agonist in comparison. 1-Ethyl-6-hydroxytryptoline was described in the scientific literature by Meghan J. Orr and colleagues in 2022. See also Substituted β-carboline List of miscellaneous serotonin 5-HT2A receptor agonists Shepherdine Pinoline Fenharmane 1-Ethyl-β-carboline References Category:5-HT2A agonists Category:5-HT2C agonists Category:Ethyl compounds Category:Hydroxyarenes Category:Tryptolines