Effect of 1-(3,4-methylenedioxyphenyl)-2-aminopropane and its optical isomers in PMMA-trained rats.
1-(3,4-Methylenedioxyphenyl)-2-aminopropane (MDA) is a drug of abuse that is known to produce stimulus effects similar to those of the stimulant phenylalkylamine (+)amphetamine and the hallucinogenic phenylalkylamine 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). Earlier, a working model was described to account for the stimulus effects produced by phenylalkylamines. Such agents can produce one or more of three distinct effects: an amphetamine effect, a DOM effect and a third effect that is typified by the agent N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA). Because MDA is known to produce two of the three effects, in the present investigation, we sought to determine if racemic MDA or either of its optical isomers could produce a PMMA-like effect in animals. Administration of S(+)MDA, R(-)MDA and (+/-)MDA to rats trained to discriminate 1.25 mg/kg of PMMA from saline vehicle under a VI 15-s schedule of reinforcement resulted in substitution in each case. (+/-)MDA and S(+)MDA were nearly equipotent and several fold more potent than R(-)MDA. The results are not only consistent with the proposed model but also identify (+/-)MDA as the first phenylalkylamine shown to produce all three types of stimulus effects (i.e., amphetamine-like, DOM-like and PMMA-like) in rats.
Glennon
Richard A
RA
Department of Medicinal Chemistry, School of Pharmacy, Box 980540, Virginia Commonwealth University, Richmond, VA 23298-0540, USA. glennon@hsc.vcu.edu
Young
Richard
R
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
C106885:paramethoxymethamphetamine; D008694:Methamphetamine; D015104:3,4-Methylenedioxyamphetamine