Effect of timiperone on 3H-spiroperidol binding to rat striatal dopamine receptors

The effects of timiperone, its metabolites and related compounds on specific 3H-spiroperidol binding to dopamine receptors in the rat corpus striatum were studied to clarify the affinity of timiperone, a new butyrophenone, for the receptors and whether timiperone itself was active in vivo. Timiperone had an approx. 0.6, 5 and 30 times greater affinity for the receptors than did spiroperidol, haloperidol and chlorpromazine, respectively. This affinity was observed specifically for antipsychotic drugs but not for diazepam and trihexyphenidyl. Timiperone metabolites had little or no affinity for the receptors. Radioreceptor assay values agreed well with the radiochemical assay for timiperone in the plasma and brain of rats after i.v. injection of the 14C-labeled drug. Thus, it is conceivable that timiperone itself exerts its potent antipsychotic activity by blockade of cerebral dopamine receptors.