IS CLOZAPINE SELECTIVE FOR THE DOPAMINE D-4 RECEPTOR

Binding of H-3-spiperone and H-3-raclopride to membranes of cells stab ly-transfected with a human dopamine D-2 receptor clone was investigat ed, as was that of H-3-spiperone to those stably-transfected with a hu man D-4 receptor clone. H-3-spiperone and H-3-raclopride labeled the s ame number of sites in the D-2 receptor preparation. The inhibition of binding by clozapine, spiperone, (-) eticlopride, haloperidol and the novel substituted benzamide 1192U90 was also investigated. Clozapine and 1199U90 showed greater inhibition of H-3-raclopride binding than H -3-spiperone binding to the D-2 receptor. Comparison with inhibition o f H-3-spiperone binding to the D-4 receptor revealed that clozapine an d 1192U90 displayed apparent selectivity (as assessed by K-i ratios) f or the D-4 receptor when compared with binding of H-3-spiperone, but n ot H-3-raclopride, to the D-2 receptor.