PET analysis of human dopamine receptor subtypes using 11C-SCH 23390 and 11C-raclopride.
Tracer doses of 11C-SCH 23390 and 11C-raclopride, selective D1-dopamine and D2-dopamine receptor antagonists, respectively, were injected intravenously into three healthy male volunteers and two drug-treated schizophrenic patients. Regional radioactivity in brain and plasma was followed during 1 h by positron emission tomography (PET). After injection of both ligands a high accumulation of radioactivity was observed in the dopamine-rich caudate putamen. Experiments with 11C-SCH 23390, but not 11C-raclopride, showed a conspicuous accumulation of radioactivity also in the neocortex. None of the ligands accumulated in the dopamine-poor cerebellum. Specific binding of 11C-raclopride in the putamen was reduced by more than 80% in schizophrenic patients treated with antipsychotic doses of sulpiride or cis(Z)-flupentixol decanoate. 11C-SCH 23390 binding was slightly reduced in both the cortex and the putamen after treatment with cis(Z)-flupentixol decanoate but not after sulpiride. The results indicate that clinical antipsychotic drug treatment with sulpiride and cis(Z)-flupentixol decanoate causes a substantial blockade of D2-dopamine receptors in the basal ganglia but has only a minor effect on D1-dopamine receptors.
D000328:Adult; D001552:Benzazepines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005475:Flupenthixol / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020891:Raclopride; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D013469:Sulpiride / Q000627:therapeutic use
D001552:Benzazepines; D002250:Carbon Radioisotopes; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C007761:flupenthixol decanoate; D020891:Raclopride; D013469:Sulpiride; D005475:Flupenthixol