(+)-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 Dec;255(3):1098-106.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Methylenedioxyamphetamine / analogs & derivatives*
  • 3,4-Methylenedioxyamphetamine / pharmacology
  • Animals
  • Behavior, Animal / drug effects*
  • Dose-Response Relationship, Drug
  • Hallucinogens / pharmacology
  • Indans / pharmacology
  • Learning / drug effects
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Rats
  • Rats, Inbred Strains
  • Stereoisomerism

Substances

  • Hallucinogens
  • Indans
  • 5,6-methylenedioxy-2-aminoindane
  • N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine
  • 5,6-methylenedioxy-2-methylaminoindan
  • 3,4-Methylenedioxyamphetamine
  • N-Methyl-3,4-methylenedioxyamphetamine