1,2,3,4-TETRAHYDROISOQUINOLINE ANALOGS OF PHENYLALKYLAMINE STIMULANTSAND HALLUCINOGENS

Conformationally constrained, 1,2,3,4-tetrahydroisoquinoline (TIQ) ana logs of central stimulant (e.g. amphetamine) and hallucinogenic (e.g. DOM) phenylalkylamines were prepared and evaluated to determine the co ntribution to activity of this conformational restriction. The ampheta mine-related TIQs failed to produce locomotor stimulation in mice and did not produce amphetamine-appropriate responding in tests of stimulu s generalization in (+)amphetamine-trained rats. Hallucinogen-related TIQs lacked appreciable affinity for 5-HT2A serotonin receptors and di d not produce DOM-like effects in tests of stimulus generalization in DOM-trained rats. It is concluded that the phenylalkylamine conformati on represented by the TIQs is not a major contributor to these actions .