A Drug Discriminative Analysis of R 79598, a New Neuroleptic

Summary

R 79598, a new potent neuroleptic, was compared with haloperidol and risperidone in a drug discrimination test procedure in rats. Generalization and antagonism studies were performed in rats trained to discriminate either LSD, DOM, d-amphetamine, cocaine or xylazine from saline. None of the three compounds produced a stimulus generalization to any of the training drugs. In terms of DOM and LSD antagonism, the relative order of potency was R 79598 ≥ risperidone > haloperidol (inactive) and for d-amphetamine it was R 79598 > haloperidol > risperidone. The three drugs were only partial cocaine antagonists and none of the drugs antagonized xylazine. All three compounds reduced response rate. Despite marked effects on response rate, R 79598 showed the greatest differentiation between drug antagonism and sedation. These results confirm R 79598 to be a very potent serotonin 5-HT₂ and dopamine D₂ antagonist.