Structure-activity studies on amphetamine analogs using drug discrimination methodology.
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.
D000470:Alkaloids / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004193:Discrimination Learning; D005795:Generalization, Stimulus; D007189:Indans / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000470:Alkaloids; D000662:Amphetamines; D007189:Indans; D013764:Tetrahydronaphthalenes; C006545:2-aminoindan; C006561:2-aminotetralin; C023665:cathinone