title: (+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine as a discriminative stimulus in studies of 3,4-methylenedioxy-methamphetamine-like behavioral activity.
abstract: The stimulus properties of 3,4-methylenedioxymethamphetamine (MDMA)-like compounds were studied in rats trained to discriminate saline from (+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine [(+)-MBDB] hydrochloride (7.18 mumol/kg; 1.75 mg/kg), the alpha-ethyl homolog of MDMA. In previous experiments with (+)-MBDB as a test drug, complete substitution was observed for MDMA but not for (+)-lysergic acid diethylamide or (+)-amphetamine. In the study reported here, the (+)-MBDB cue generalized to MDMA and the parent drug, 3,4-methylenedioxyamphetamine. All three drugs exhibited a similar stereoselectivity, the (+)-isomer having potency greater than the (-)-isomer. By contrast, the hallucinogens, (+)-lysergic 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 hallucinogens and stimulants and may represent the effects of a novel drug class, given the name entactogens. Although the mechanism of action for the discriminative stimulus properties of MDMA-like compounds is not known, there is evidence that presynaptic serotonergic, but not dopaminergic, mechanisms are critical. Finally, 5,6-methylenedioxy-2-aminoindan a non-neurotoxic 3,4-methylenedioxyamphetamine rigid analog that was previously found to substitute for MDMA but not for (+)-lysergic acid diethylamide was found in the study described here to substitute completely for (+)-MBDB. The N-methyl derivative 5,6-methylenedioxy-2-methylminoindan produced similar results. 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.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana.
authors.forename: R
authors.initials: R
authors.lastname: Oberlender
authors.forename: D E
authors.initials: DE
authors.lastname: Nichols
mesh_terms: D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006213:Hallucinogens / Q000494:pharmacology; D007189:Indans / Q000494:pharmacology; D007858:Learning / Q000187:drug effects; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
chemical_list: D006213:Hallucinogens; D007189:Indans; C066678:5,6-methylenedioxy-2-aminoindane; C051570:N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine; C066679:5,6-methylenedioxy-2-methylaminoindan; D015104:3,4-Methylenedioxyamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine