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Lipophilicity and serotonin agonist activity in a series of 4-substituted mescaline analogs

David E. Nichols, Donald C. Dyer

Journal of Medicinal Chemistry February 1, 1977 DOI: 10.1021/jm00212a022 via OpenAlex

Summary

AI-generated from the abstract

Replacing the 4-methoxy group of mescaline with larger alkyl groups or bromine increases activity at serotonin receptors in a sheep umbilical artery preparation. This increase correlates with lipophilicity, measured by 1-octanol-water partition coefficients, but activity declines when the 4-substituent reaches about five atoms in length. The findings suggest that a 3,4,5-trisubstituted pattern may be more effective than a 2,4,5-substitution pattern for receptor activity.

Study at a glance

Characteristics Experimental study Peer reviewed
Population Sheep umbilical artery preparation
Topics Mescaline Serotonin
Keywords Lipophilicity Stereochemistry Serotonin agonist Pharmacology
Citations 23
Key finding Replacing the 4-methoxy of mescaline with higher alkyl homologues or bromine increases serotonin receptor activity, which correlates with lipophilicity, but activity drops when the 4-substituent is about five atoms long.

Abstract

Replacement of the 4-methoxy of mescaline with higher alkyl homologues or with bromine led to increased activity at serotonin receptors in a sheep umbilical artery preparation. This activity appears correlated with lipophilicity, as measured by 1-octanol-water partition coefficients, but drops off when the 4-substituent is about five atoms in length. It is suggested that 3,4,5-trisubhe 2,4,5-substitution pattern.

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