D1- and D2-dopamine receptor occupancy during treatment with conventional and atypical neuroleptics.
Using positron emission tomography and the selective ligands 11C-SCH23390 and 11C-raclopride, central D1- and D2-dopamine receptor occupancy was determined in schizophrenic patients treated with clinical doses of classical and atypical neuroleptics. Treatment with ten chemically distinct classical neuroleptics resulted in a 65-89% occupancy of D2-dopamine receptors. This finding represents strong support for the hypothesis that the mechanism of action of antipsychotic drugs is indeed related to a substantial degree of D2-dopamine receptor occupancy. In two patients treated with the atypical neuroleptic clozapine, 300 mg b.i.d. and 150 mg b.i.d., the D2-dopamine receptor occupancy was 65 and 40%, respectively. D1-dopamine receptor occupancy was determined in six antipsychotic drug-treated patients. No D1-dopamine receptor occupancy was found in patients treated with sulpiride and perphenazine, compounds known to be selective D2-dopamine receptor antagonists. The highest D1-dopamine receptor occupancy, 42%, was found in the patient treated with clozapine 150 mg b.i.d. The effects of the atypical neuroleptic clozapine may be related to a combined effect on both D1- and D2-dopamine receptors.
Farde
L
L
Department of Psychiatry and Psychology, Karolinska Institutet, Stockholm, Sweden.
Wiesel
F A
FA
Nordström
A L
AL
Sedvall
G
G
D014150:Antipsychotic Agents / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000378:metabolism; D006801:Humans; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology; D011954:Receptors, Dopamine / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine