1-(2,4,5-Trimethoxyphenyl)-6-chlorotryptoline, also known as 6-chloro-1-(2,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-β-carboline, is a serotonin receptor modulator of the β-carboline family. It is a ring-substituted derivative of the β-carboline tryptoline (THβC) and a simplified analogue of the heteroyohimbine alkaloid alstonine.
Pharmacology Pharmacodynamics 1-(2,4,5-Trimethoxyphenyl)-6-chlorotryptoline acts as a highly potent full agonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors. Its () values were 1.7nM (98.4%) at the serotonin 5-HT2A receptor, 0.50nM (97.5%) at the serotonin 5-HT2B receptor, and 0.58nM (96.7%) at the serotonin 5-HT2C receptor. The drug was one of the most potent serotonin 5-HT2A receptor agonists of a large series of assessed tryptoline derivatives.
1-(2,4,5-Trimethoxyphenyl)-6-chlorotryptoline's potent serotonin 5-HT2 receptor agonism is in notable contrast to other simpler β-carbolines like harmine and harmaline, which have been found to be inactive as serotonin 5-HT2A receptor agonists even at very high concentrations. Similarly, tryptoline itself shows very low affinity for serotonin 5-HT2 receptors.
In addition to the serotonin 5-HT2 receptors, 1-(2,4,5-trimethoxyphenyl)-6-chlorotryptoline shows variable but mostly high affinity for most other serotonin receptors (Ki = 2.50–1,493nM). Interactions at other receptors have also been reported.
Chemistry Synthesis The chemical synthesis of 1-(2,4,5-trimethoxyphenyl)-6-chlorotryptoline has been described.
Analogues A large number of analogues of 1-(2,4,5-trimethoxyphenyl)-6-chlorotryptoline have been described.
History 1-(2,4,5-Trimethoxyphenyl)-6-chlorotryptoline was first 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 1-Ethyl-6-hydroxytryptoline Pinoline NU-1223 LY-266,097 LY-272,015 Fenharmane
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