PMMA-stimulus generalization to the optical isomers of MBDB and 3,4-DMA.
J B Rangisetty, M L Bondarev, J Chang-fong, R Young, R A Glennon
Pharmacology, biochemistry, and behavior January 1, 2001 Peer reviewed DOI: 10.1016/s0091-3057(01)00530-5 via PubMed
Summary
The study found that several psychoactive phenylisopropylamines, including PMMA, S(+)-MBDB, R(-)-MBDB, S(+)-3,4-DMA, and R(-)-3,4-DMA, produce similar stimulus effects in rats. The effective doses for these agents varied, with PMMA having an ED(50) of 0.4 mg/kg and S(+)-MBDB at 0.8 mg/kg. The findings clarify the PMMA stimulus and the structural characteristics required for such effects.
Study at a glance
| Population | rats trained to discriminate between drugs and vehicle |
|---|---|
| Key finding | PMMA and various phenylisopropylamines produce common stimulus effects in rats. |
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.