PMMA-stimulus generalization to the optical isomers of MBDB and 3,4-DMA.

Psychoactive phenylisopropylamines can produce different stimulus effects in animals, typified by hallucinogen DOM, stimulant amphetamine, and the less understood agent PMMA. In rats trained to discriminate PMMA from vehicle, the PMMA stimulus generalized to both optical isomers of MBDB and 3,4-DMA, with S(+)-MBDB (ED50=0.8 mg/kg) more potent than R(-)-MBDB (2.0 mg/kg) and S(+)-3,4-DMA (2.6 mg/kg) more potent than R(-)-3,4-DMA (3.9 mg/kg). These agents produce stimulus effects similar to PMMA. Both isomers of 3,4-DMA substituted for an MDMA stimulus but not for DOM or amphetamine stimuli. The evidence suggests PMMA, both isomers of MBDB and 3,4-DMA, and S(+)-MDMA produce common stimulus effects in rats, better defining the PMMA stimulus and structural requirements for this effect.

Study at a glance

Abstract

Psychoactive phenylisopropylamines can produce one or more of several different stimulus effects in animals. These effects are typified by the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), the central stimulant amphetamine, and by N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA), an agent whose actions are not yet well understood. The optical isomers of two phenylisopropylamines known to lack DOM and amphetamine-stimulus character, that is N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminobutane (MBDB) and 1-(3,4-dimethoxyphenyl)-2-aminopropane (3,4-DMA), were examined in rats trained to discriminate 1.25 mg/kg of PMMA from vehicle. The PMMA stimulus (ED(50)=0.4 mg/kg) generalized to all four agents: S(+)-MBDB (ED(50)=0.8 mg/kg), R(-)-MBDB (ED(50)=2.0 mg/kg), S(+)-3,4-DMA (ED(50)=2.6 mg/kg) and R(-)-3,4-DMA (ED(50)=3.9 mg/kg). The results show that these agents produce stimulus effects similar to those produced by PMMA. Both isomers of MBDB have been previously demonstrated to substitute for N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) in rats trained to discriminate MDMA from vehicle, but MBDB-trained animals failed to recognize DOM or amphetamine. Similar results were obtained with the 3,4-DMA optical isomers in the present investigation using rats trained to discriminate MDMA, DOM or (+)-amphetamine from vehicle; both isomers of 3,4-DMA substituted for an MDMA stimulus, but not for a DOM or amphetamine stimulus. Taken together, the evidence suggests that PMMA, S(+)-MBDB, R(-)-MBDB, S(+)-3,4-DMA, R(-)-3,4-DMA, and S(+)-MDMA can produce common stimulus effects in rats. The present findings also better define the PMMA stimulus and the structural requirements necessary to produce this type of stimulus effect.