title: PMMA-stimulus generalization to the optical isomers of MBDB and 3,4-DMA.
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.
authors: Department of Medicinal Chemistry, School of Pharmacy, Box 980540, Virginia Commonwealth University, Richmond, VA 23298-0540, USA.
authors: J B
authors: JB
authors: Rangisetty
authors: M L
authors: ML
authors: Bondarev
authors: J
authors: J
authors: Chang-Fong
authors: R
authors: R
authors: Young
authors: R A
authors: RA
authors: Glennon
mesh_terms: D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000494:pharmacology; D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005795:Generalization, Stimulus / Q000187:drug effects*; D007536:Isomerism; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D000662:Amphetamines; D000697:Central Nervous System Stimulants; D017366:Serotonin Receptor Agonists; C106885:paramethoxymethamphetamine; C051570:N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine; C014500:3,4-dimethoxyamphetamine; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D008694:Methamphetamine; D015104:3,4-Methylenedioxyamphetamine; D003913:Dextroamphetamine