Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: a double-blind PET study of schizophrenic patients.
The relationship between central D2-dopamine receptor occupancy and antipsychotic drug effects was examined in a double-blind study. Raclopride was the compound used to induce a selective occupancy of the D2-dopamine receptors. In addition, 11C-labeled raclopride was the radioligand used to measure occupancy by positron emission tomography (PET). Seventeen schizophrenic patients were randomly assigned to one of three parallel groups treated for 4 weeks with daily doses of 2, 6, or 12 mg of raclopride. D2-receptor occupancy was determined by PET at steady-state conditions in 13 patients who completed the study. A statistically significant relationship was demonstrated between antipsychotic effect and degree of D2-receptor occupancy (p < 0.05). Patients with extrapyramidal side effects had significantly higher D2-receptor occupancy than those without (p = 0.02). The finding of a relationship between selective occupancy of the D2-dopamine receptors and clinical effects in schizophrenic patients principally provides new support for the dopamine hypothesis of antipsychotic drug action.
Nordström
A L
AL
Department of Psychiatry and Psychology, Karolinska Institute, Stockholm, Sweden.
Farde
L
L
Wiesel
F A
FA
Forslund
K
K
Pauli
S
S
Halldin
C
C
Uppfeldt
G
G
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging*; D065127:Dopamine D2 Receptor Antagonists; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012457:Salicylamides / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000188:drug therapy; D012565:Schizophrenic Psychology; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride