Perlapine and dopamine metabolism: prediction of antipsychotic efficacy

A model for the prediction of antipsychotic efficacy based on the dose-dependent increase in levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum and tuberculum olfactorium of the rat is presented. The effect of perlapine, a sleep-promoting and sedative agent reported to lack antipsychotic efficacy, was compared in this system to haloperidol, chlorpromazine and clozapine. All four drugs produced a dose-dependent increase in DOPAC in the two dopamine-rich structures. The potency of perlapine was similar to that of chlorpromazine. Dopamine, assayed in the striatum and tuberculum olfactorium by a new gas chromatographic procedure was not altered by perlapine. The time--action curves for perlapine and clozapine were virtually identical both in the striatum and in the tuberculum olfactorium. All four drugs also elevated homovanillic acid to a similar extent. These results indicate that perlapine should be re-evaluated clinically. We predict that such trials will reveal that perlapine does possess antipsychotic efficacy.