Positron emission tomography studies on D2 dopamine receptor occupancy and plasma antipsychotic drug levels in man.
Positron emission tomography (PET) and the selective radioligand [11C]raclopride were used to measure D2 receptor occupancy in several studies in schizophrenic patients and healthy subjects. Clinical effects of the treatment were recorded, and drug plasma concentrations measured. The hypothesized curvilinear relationship between receptor occupancy and drug plasma concentrations was supported experimentally. We suggest that there may be a distinct threshold for antipsychotic effect at about 70% D2 receptor occupancy, and another threshold for extrapyramidal side effects above 80% D2 receptor occupancy. Receptor occupancy was high even at low plasma drug concentrations. Our data indicate a need to establish dose-response curves for the conventional neuroleptics. Such a dose-response relationship might be expected for a much lower dose interval than those previously examined.
Nyberg
S
S
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Nordström
A L
AL
Halldin
C
C
Farde
L
L
D014150:Antipsychotic Agents / Q000097:blood*; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D006220:Haloperidol