IS CLOZAPINE SELECTIVE FOR THE DOPAMINE D-4 RECEPTOR

Binding of H-3-spiperone and H-3-raclopride to membranes of cells stably-transfected with a human dopamine D-2 receptor clone was investigated, as was that of H-3-spiperone to those stably-transfected with a human D-4 receptor clone. H-3-spiperone and H-3-raclopride labeled the same 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 of H-3-spiperone binding to the D-4 receptor revealed that clozapine and 1192U90 displayed apparent selectivity (as assessed by K-i ratios) for the D-4 receptor when compared with binding of H-3-spiperone, but not H-3-raclopride, to the D-2 receptor.