Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class

A new phenethylamine derivative, 1-(1,3-benzodioxol-5-yl)-2-butanamine, was synthesized in both racemic and enantiomerically pure forms, along with the related compound MDA. In rats trained to discriminate LSD from saline, only the racemate and R-(-) enantiomer of the alpha-methyl homologue, and the S-(+) enantiomer of the alpha-ethyl primary amine, produced stimulus generalization; other enantiomers and N-methyl derivatives did not. Human studies indicated the N-methyl derivative was nonhallucinogenic but had a novel psychoactive effect. The authors propose this compound as the prototype of a new pharmacological class, termed entactogens, potentially useful in facilitating psychotherapy.

Study at a glance

Abstract

The alpha-ethyl phenethylamine derivative 1-(1,3-benzodioxol-5-yl)-2-butanamine was prepared. An asymmetric synthesis was used to prepare the enantiomers of this compound and the related alpha-methyl homologue (MDA). The racemates and enantiomers of both compounds were evaluated in the two-lever drug discrimination assay in rats trained to discriminate saline from 0.08 mg/kg of LSD tartrate. Stimulus generalization occurred with the racemate and the R-(-) enantiomer of the alpha-methyl homologue and the S-(+) enantiomer of the alpha-ethyl primary amine. No generalization occurred with the other enantiomers or with the N-methyl derivatives of either series. Human psychopharmacology studies revealed that the N-methyl derivative of the title compound was nonhallucinogenic and that it had a new, novel psychoactive effect. It is suggested that this compound is the prototype of a new pharmacologic class that may have value in facilitating psychotherapy and that this class be designated as entactogens.