POSITRON EMISSION TOMOGRAPHY STUDIES ON D-2 AND 5-HT2 RECEPTOR-BINDING IN RISPERIDONE-TREATED SCHIZOPHRENIC-PATIENTS

By the use of positron emission tomography (PET), high central dopamin e D-2 receptor occupancy (70 to 90%) has been demonstrated in patients treated with conventional neuroleptics. In patients treated with the atypical antipsychotic clozapine, the D-2 occupancy was low (20 to 67% ). The effects of clozapine may thus be mediated by a mechanism distin ct from D-2 occupancy, The observation that low doses of clozapine (12 5 to 175 mg daily) induced more than 80% (5-hydroxytryptamine) 5-HT2 o ccupancy supports the view that 5-HT2 antagonism may be related to the atypical effects of clozapine. Risperidone is a new antipsychotic dru g with high affinity in vitro for both central 5-HT2 and D-2 receptors . In this study, me determined the D-2 and 5-HT2 occupancy induced by clinical treatment with risperidone. Four patients with acute exacerba tion of schizophrenia were examined by PET after 4 weeks of treatment with risperidone, 6 mg daily. The D-2 occupancy in the striatum was 75 to 80%. The 5-HT2 occupancy in the neocortex was 78 to 88%. This stud y confirms that, in patients with schizophrenia, treatment with risper idone induces a high D-2 and 5-HT2 occupancy. Risperidone is, accordin gly, a suitable drug for the examination of the clincial benefit of co mbined serotonin and dopamine antagonism.