Positron emission tomography studies on D2 and 5-HT2 receptor binding in risperidone-treated schizophrenic patients.
By the use of positron emission tomography (PET), high central dopamine D2 receptor occupancy (70 to 90%) has been demonstrated in patients treated with conventional neuroleptics. In patients treated with the atypical antipsychotic clozapine, the D2 occupancy was low (20 to 67%). The effects of clozapine may thus be mediated by a mechanism distinct from D2 occupancy. The observation that low doses of clozapine (125 to 175 mg daily) induced more than 80% (5-hydroxytryptamine) 5-HT2 occupancy supports the view that 5-HT2 antagonism may be related to the atypical effects of clozapine. Risperidone is a new antipsychotic drug with high affinity in vitro for both central 5-HT2 and D2 receptors. In this study, we determined the D2 and 5-HT2 occupancy induced by clinical treatment with risperidone. Four patients with acute exacerbation of schizophrenia were examined by PET after 4 weeks of treatment with risperidone, 6 mg daily. The D2 occupancy in the striatum was 75 to 80%. The 5-HT2 occupancy in the neocortex was 78 to 88%. This study confirms that, in patients with schizophrenia, treatment with risperidone induces a high D2 and 5-HT2 occupancy. Risperidone is, accordingly, a suitable drug for the examination of the clinical benefit of combined serotonin and dopamine antagonism.
Farde
L
L
Department of Psychiatry and Psychology, Karolinska Hospital, Stockholm, Sweden.
Nyberg
S
S
Oxenstierna
G
G
Nakashima
Y
Y
Halldin
C
C
Ericsson
B
B
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001665:Binding Sites; D001921:Brain / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D018967:Risperidone; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D007555:Isoxazoles; D010880:Piperidines; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D018967:Risperidone