Oberlender R, Nichols DE.
“(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine as a discriminative stimulus in studies of 3,4-methylenedioxy-methamphetamine-like behavioral activity”.
J Pharmacol Exp Ther. 1990;255(3):1098-106.
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Abstract
The stimulus properties of 3,4-methylenedioxymethamphetamine (MDMA) Like compounds were studied in rats trained to discriminate saline from (+)-N-methyl-l-(1,3-benzodioxol-5-yl)-2-butanamine [(+)-MBDB] hydrochloride (7.18/zmol/kg; 1.75 mg/kg), the _-ethyl homolog of MDMA. In previous experiments with (+)-MBDB as a test drug, complete substitution was observed for MDMA but not for (+)-Iysergic acid diethylamide or (+)-neuro-amphetamine. In the study reported here, the (+)-MBDB cue to generalized to MDMA and the parent drug, 3,4-methylenedi-oxyamphetamine. All three drugs exhibited a similar stereoselectivity, the (+)-isomer having potency greater than the (-)-isomer. By contrast, the hallucinogens, (+)-Iysergic acid diethylamide, 2,5-dimethoxy-4-methylamphetamine and mescaline and the psychostimulants (+)-amphetamine and methamphetamine did not substitute for (+)-MBDB. Cocaine produced partial substitution. The results support the hypothesis that the primary-(+)-behavioral activity of MDMA-like compounds is unlike that of hallucinogensand stimulants and may represent the effects of a novel drug class, given the name entactogens. Although the mechanismof action for the discriminative stimulus properties of MDMA-like compounds is not known, there is evidence that presynapticserotonergic, but not dopaminergic, mechanisms are critical. Finally, 5,6-methylenedioxy-2-aminoindan a non-neurotoxic 3,4-methylenedioxyamphetaminerigid analog that was previously found to substitute for MDMA but not for (+)-Iysergicacid diethylamide was found in the study described here to substitute completely for (+)-MBDB. The N-methyl derivative 5,6-methylenedioxy-2-methylaminoindan produced similar resuits. The demonstration of entactogen-like discriminative stimulus properties, for drugs devoid of neuronal degenerative toxicity potential, serves as evidence of the independent mechanisms for these effects in rats.
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