BINDING OF ANTIPSYCHOTIC-DRUGS AT ALPHA(1A)-ADRENOCEPTORS AND ALPHA(1B)-ADRENOCEPTORS - RISPERIDONE IS SELECTIVE FOR THE ALPHA(1B)-ADRENOCEPTORS

The binding of the antipsychotic drugs risperidone, (+)-butaclamol, clozapine, haloperidol, spiperone, thioridazine and YM-09151-2 was studied at the subtypes of the alpha1-adrenoceptor. Saturation experiments showed that [H-3]prazosin labelled a single population of binding sites in the spleen (alpha1B) and hippocampus (alpha1A and alpha1B) (dissociation constants (K(D)): 0.26 nM and 0.14 nM respectively). Prazosin displaced the radioligand in a monophasic manner in both the spleen and hippocampus whereas 5-methyl-urapidil, phentolamine and WB 4101 displaced the radioligand in a monophasic manner in the spleen but in a biphasic manner in the, hippocampus. The affinity of these three compounds for the low affinity site in the hippocampus was similar to that observed in the spleen, suggesting that all three were selective for the alpha1A-adrenoceptor. Furthermore, the affinities for the alpha1A- and alpha1B-adrenoceptors calculated in this manner were in agreement with literature values. With the exception of risperidone, all the antipsychotic drugs tested failed to show selectivity for either of the alpha1-adrenoceptor subtypes. Risperidone was 120-fold more selective for the alpha1B-adrenoceptor with respect to the alpha1A-adrenoceptor (K(i) values: 2.3 +/- 1.2 nM and 283.6 +/- 174.1 nM respectively).