Demethyl analogs of psychoactive methoxyphenalkylamines: synthesis and serotonin receptor affinities

Abstract

Mono-O-demethylation of several 2,5-dimethoxyphenalkylamines increases their affinity for the serotonin receptors of the isolated rat fundus preparation. Demethylation of methoxyphenalkylamines results in compounds which produce an antagonism which is not of a competitive nature. With respect to 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), demethylation of the 2-methoxy group alters affinity in a manner which parallels that observed upon demethylation of 5-methoxy-N, N-dimethyltryptamine. Using a discriminative stimulus paradigm, behavioral studies with rats reveal that the 2-hydroxy analog but not the 5-hydroxy analog of DOM produces effects (interoceptive cues) similar to those produced by 5-methoxy-N,N-dimethyltryptamine.