Discriminative stimulus properties of alpha-ethyltryptamine optical isomers

alpha -Ethyltryptamine (alpha -ET) possesses central stimulant and hallucin ogenic activity. Also, in tests of stimulus generalization using rats train ed to discriminate the controlled substance analog (i.e., designer drug) N- methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) from vehicle, alp ha -ET substituted for MDMA. These previous studies employed racemic alpha -ET. Because psychoactive phenylalkylamines with abuse potential can produc e one or more of three distinct stimulus effects (i.e., amphetamine-, DOM- and/or PMMA-like effects) in animals trained to discriminate either the sti mulant (+)amphetamine, the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2- aminopropane (DOM), or N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA) f rom vehicle, and because these effects can be stereoselective, the individu al optical isomers of alpha -ET were examined in groups of animals trained to discriminate (+)amphetamine, DOM, PMMA and MDMA from saline vehicle. (-) alpha -ET (ED50 = 7.8 mg/kg), but not (+)alpha -ET (maximum of 53% drug-app ropriate responding), substituted for (+)amphetamine, whereas (+)alpha -ET (ED50 = 2.7 mg/kg), but not (-)alpha -ET (maximum of 33% drug-appropriate r esponding), substituted for DOM. Both optical isomers of alpha -ET substitu ted for PMMA and MDMA with ED50 values of 1.6 and 1.4 mg/kg (PMMA-trained a nimals) 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 b oth optical isomers of alpha -ET are capable of producing an MDMA/PMMA-like effect at nearly comparable doses, and that the stimulant or amphetamine-l ike nature of alpha -ET resides primarily with its ( -)isomer whereas hallu cinogenic or DOM-like character resides primarily with the (+)enantiomer. ( C) 2001 Elsevier Science Inc. All rights reserved.