Antipsychotics lack α1A/B adrenoceptor subtype selectivity in the rat

The α1A- and α1B-adrenoceptor affinity of the typical (chlorpromazine, haloperidol, pimozide, thioridazine and trifluoperazine) and atypical (clozapine, olanzapine, quetiapine, risperidone and sertindole) antipsychotics was determined by competition binding at α1A- and α1B-adrenoceptors in rat submaxillary gland and liver. Although all antipsychotics bound to both subtypes with relatively high affinity (Kis<74 nM), none were selective (>10-fold). Comparison with published dopamine D2 receptor affinities suggests that antipsychotic blockade of α1A- and/or α1B-adrenoceptors may contribute to the antipsychotic activity of all the atypical and several of the typical antipsychotics examined.