Chemistry:1-Ethyl-6-hydroxytryptoline

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1-Ethyl-6-hydroxytryptoline (1-Et-6-OH-THβC) is a serotonin 5-HT2 receptor agonist of the β-carboline family related to tryptoline.[1] It is the 1-ethyl and 6-hydroxy derivative of tryptoline.[1]

The drug has been found to act as a potent agonist of the serotonin 5-HT2A and 5-HT2C receptors, with EC50 (Emax) values of 195 nM (85%) and 61 nM (98%) in terms of Gq-mediated calcium flux, respectively.[1] This is in notable contrast to other β-carbolines like harmine and harmaline, which are inactive as serotonin 5-HT2A receptor agonists.[2][3][4] It is also in apparent contrast to tryptoline, which shows very low affinity for the serotonin 5-HT2A receptor (Ki = 3,900 nM[5] and is inactive as an agonist of the serotonin 5-HT2B receptor (KB = >3,000 nM).[6]

The chemical synthesis of 1-ethyl-6-hydroxytryptoline has been described.[1]

1-Ethyl-6-hydroxytryptoline was described in the scientific literature by Meghan J. Orr and colleagues.[1]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "Discovery of Highly Potent Serotonin 5-HT2 Receptor Agonists Inspired by Heteroyohimbine Natural Products". ACS Medicinal Chemistry Letters 13 (4): 648–657. April 2022. doi:10.1021/acsmedchemlett.1c00694. PMID 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". 
  2. ↑ "5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens". Pharmacology, Biochemistry, and Behavior 72 (1–2): 29–37. May 2002. doi:10.1016/s0091-3057(01)00720-1. PMID 11900766. 
  3. ↑ "Examining Ayahuasca Constituents at 5-HT2A Receptors in Search of Antidepressant Action". 3 May 2022. https://scholarscompass.vcu.edu/etd/6884/. 
  4. ↑ "Binding of beta-carbolines at 5-HT(2) serotonin receptors". Bioorganic & Medicinal Chemistry Letters 13 (24): 4421–4425. December 2003. doi:10.1016/j.bmcl.2003.09.027. PMID 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.". 
  5. ↑ "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. April 1993. PMID 8321880. 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. 
  6. ↑ "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. July 1996. doi:10.1021/jm960062t. PMID 8709108. 



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