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

Psychoactive phenylisopropylamines can produce one or more of several diffe rent stimulus effects in animals. These effects are typified by the halluci nogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), the central st imulant amphetamine, and by N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PM MA), an agent whose actions are not yet well understood. The optical isomer s of two phenylisopropylamines known to lack DOM and amphetamine-stimulus c haracter, that is N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminobutane (MBDB ) and 1-(3,4-dimethoxyphenyl)-2-aminopropane (3,4-DMA), were examined in ra ts trained to discriminate 1.25 mg/kg of PMMA from vehicle. The PMMA stimul us (ED50 = 0.4 mg/kg) generalized to all four agents: S(+)-MBDB (ED50 = 0.8 mg/kg), R(-)-MBDB (ED50 = 2.0 mg/kg), S(+)-3,4-DMA (ED50 = 2.6 mg/kg) and R(-)-3,4-DMA (ED50 = 3.9 mg/kg). The results show that these agents produce stimulus effects similar to those produced by PMMA. Both isomers of MBDB h ave been previously demonstrated to substitute for N-methyl-1-(3,4-methylen edioxyphenyl)-2-aminopropane (MDMA) in rats trained to discriminate MDMA fr om vehicle, but MBDB-trained animals failed to recognize DOM or amphetamine . Similar results were obtained with the 3,4-DMA optical isomers in the pre sent investigation using rats trained to discriminate MDMA, DOM or (+)-amph etamine from vehicle; both isomers of 3,4-DMA substituted for an MDMA stimu lus, but not for a DOM or amphetamine stimulus. Taken together, the evidenc e 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 neces sary to produce this type of stimulus effect. (C) 2001 Elsevier Science Inc . All rights reserved.