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SAR of psilocybin analogs: Discovery of a selective 5-HT2C agonist

Howard Sard, Govindaraj Kumaran, Cynthia Morency, Bryan L. Roth, Beth Ann Toth, Ping He, Louis Shuster

Bioorganic & Medicinal Chemistry Letters August 3, 2005 DOI: 10.1016/j.bmcl.2005.06.104 via OpenAlex

Summary

AI-generated from the abstract

A structure-activity relationship study of psilocybin and psilocin derivatives found that 1-methylpsilocin acts as a selective agonist at the human 5-HT(2C) receptor. Its phosphate derivative, 1-methylpsilocybin, and 4-fluoro-N,N-dimethyltryptamine each showed efficacy in an animal model of obsessive-compulsive disorder. These findings point to a new avenue for developing novel 5-HT(2C) receptor agonists with potential applications in drug discovery.

Study at a glance

Characteristics Structure-activity relationship study Peer reviewed
Interventions 1-methylpsilocybin 4-fluoro-N N-dimethyltryptamine
Topics Psilocybin
Keywords Agonist Pharmacology Hallucinogen Drug discovery
Citations 78
Key finding 1-methylpsilocin is a selective agonist at the h5-HT(2C) receptor, and both 1-methylpsilocybin and 4-fluoro-N,N-dimethyltryptamine show efficacy in an animal model for obsessive-compulsive disorder.

Abstract

An SAR study of psilocybin and psilocin derivatives reveals that 1-methylpsilocin is a selective agonist at the h5-HT(2C) receptor. The corresponding phosphate derivative, 1-methylpsilocybin, shows efficacy in an animal model for obsessive-compulsive disorder, as does 4-fluoro-N,N-dimethyltryptamine. These results suggest a new area for development of novel 5-HT(2C) agonists with applications for drug discovery.

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