Psychopharmacology

, Volume 99, Supplement 1, pp S28–S31

D1- and D2-dopamine receptor occupancy during treatment with conventional and atypical neuroleptics

  • L. Farde
  • F. A. Wiesel
  • A. L. Nordström
  • G. Sedvall
Article

DOI: 10.1007/BF00442555

Cite this article as:
Farde, L., Wiesel, F.A., Nordström, A.L. et al. Psychopharmacology (1989) 99: S28. doi:10.1007/BF00442555

Abstract

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 teh 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 drugtreated 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.

Key words

Positron Emission TomographyDopamine receptor subtypesAntipsychotic drug treatmentClozapine

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • L. Farde
    • 1
  • F. A. Wiesel
    • 1
  • A. L. Nordström
    • 1
  • G. Sedvall
    • 1
  1. 1.Department of Psychiatry and PsychologyKarolinska InstitutetStockholmSweden