Discriminative stimulus properties of alpha-ethyltryptamine optical isomers.

Abstract

alpha-Ethyltryptamine (alpha-ET) possesses central stimulant and hallucinogenic activity. Also, in tests of stimulus generalization using rats trained to discriminate the controlled substance analog (i.e., designer drug) N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) from vehicle, alpha-ET substituted for MDMA. These previous studies employed racemic alpha-ET. Because psychoactive phenylalkylamines with abuse potential can produce one or more of three distinct stimulus effects (i.e., amphetamine-, DOM- and/or PMMA-like effects) in animals trained to discriminate either the stimulant (+)amphetamine, the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), or N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA) from vehicle, and because these effects can be stereoselective, the individual optical isomers of alpha-ET were examined in groups of animals trained to discriminate (+)amphetamine, DOM, PMMA and MDMA from saline vehicle. (-)alpha-ET (ED(50)=7.8 mg/kg), but not (+)alpha-ET (maximum of 53% drug-appropriate responding), substituted for (+)amphetamine, whereas (+)alpha-ET (ED(50)=2.7 mg/kg), but not (-)alpha-ET (maximum of 33% drug-appropriate responding), substituted for DOM. Both optical isomers of alpha-ET substituted for PMMA and MDMA with ED(50) values of 1.6 and 1.4 mg/kg (PMMA-trained animals) and 1.3 and 2.0 mg/kg (MDMA-trained animals) for (-)alpha-ET and (+)alpha-ET, respectively. The results of this investigation suggest that both optical isomers of alpha-ET are capable of producing an MDMA/PMMA-like effect at nearly comparable doses, and that the stimulant or amphetamine-like nature of alpha-ET resides primarily with its (-)isomer whereas hallucinogenic or DOM-like character resides primarily with the (+)enantiomer.