Structure-activity studies on amphetamine analogs using drug discrimination methodology

Pharmacol Biochem Behav. 1984 Dec;21(6):895-901. doi: 10.1016/s0091-3057(84)80071-4.

Abstract

Animals (rats) trained to discriminate 1.0 mg/kg of S(+)-amphetamine sulfate from saline, using a standard operant training procedure, were administered doses of various amphetamine analogs in tests of stimulus generalization in order to study structure-activity relationships (SAR). The types of structural variation of the amphetamine molecule that were investigated included (a) benz-fusion of the aromatic nucleus, (b) alpha-demethylation of the alkyl side chain, (c) conversion of the benzylic methylene to a carbonyl group, and (d) conformational restriction of the side chain. Benz-fusion and alpha-demethylation appear to have a detrimental effect on activity in that none of these analogs produced amphetamine-appropriate responding. However, the carbonylated analog, i.e., cathinone, was found to be equipotent with amphetamine. Furthermore, as with amphetamine, the S-isomer of cathinone was found to be more active than its enantiomer. With respect to the conformationally-restricted analogs, the most potent compound was 2-aminotetralin which was about half as active as racemic amphetamine.

Publication types

  • Comparative Study

MeSH terms

  • Alkaloids / pharmacology
  • Amphetamines / pharmacology*
  • Animals
  • Chemical Phenomena
  • Chemistry
  • Discrimination Learning
  • Generalization, Stimulus
  • Indans / pharmacology
  • Male
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship
  • Tetrahydronaphthalenes / pharmacology

Substances

  • Alkaloids
  • Amphetamines
  • Indans
  • Tetrahydronaphthalenes
  • 2-aminoindan
  • 2-aminotetralin
  • cathinone