N-Methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA) and N-Methyl-1-(34-methylenedioxyphenyl)-2-aminopropane (MDMA) Produce Nonidentical Discriminative Stimuli in Rats

摘要

N-Methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (methylenedioxy- methamphetamine, MDMA, Ecstasy) and its structurally abbreviated congener N-methyl-1-(4-methoxyphenyl)-2-aminopropane (para-methoxymethamphetamine, PMMA) are chemically related designer drugs, and PMMA is sometimes sold on the clandestine market as a substitute for MDMA. Prior drug discrimination studies have found that MDMA and PMMA substitute for one another suggesting that they produce similar discriminative stimulus effects in rats. However, there also are some indications that the two agents produce distinct stimulus effects. In this study, further comparisons were made between the stimulus effects of these two agents. Sprague-Dawley rats were trained to discriminate either 1.25 mg/kg of PMMA or 1.5 mg/kg of MDMA from saline vehicle in a two-lever operant paradigm. A structure-activity comparison revealed that MDMA and PMMA behave similarly upon homologation of their terminal amine substituents. In contrast, the PMMA stimulus, unlike an MDMA stimulus, failed to generalize completely to the psychostimulant cocaine, 8-hydroxy-2-(N, N-di-n-propylamino)tetralin (8-OH DPAT), and R(−)-1-(3-methoxyphenyl)-2-aminopropane [R(−)MMA]. In an additional group of animals, a (+)amphetamine stimulus partially generalized to R(−)MMA. Taken together, the results argue and re-emphasize the conclusion that the stimulus effects produced by MDMA and PMMA are similar, but non-identical, and that PMMA is the less “stimulant-like” of the two.