SEROTONIN-2 AND DOPAMINE-1 BINDING-COMPONENTS OF CLOZAPINE IN FRONTAL-CORTEX AND STRIATUM IN THE HUMAN BRAIN VISUALIZED BY POSITRON EMISSION TOMOGRAPHY

The specific binding of IV-methyl-C-11-clozapine in the human brain wa s studied in five healthy volunteers with positron emission tomography (PET). Four of the volunteers were reexamined after treatment with th e dopamine D-1 and D-2 receptor antagonist flupenthixol, and all five volunteers were reexamined after pretreatment with the serotonin(2) re ceptor antagonist ritanserin. The examinations after flupenthixol and ritanserin treatment were performed on different occasions. In the flu penthixol part of the study, two of the subjects were given an oral do se of 1 mg flupenthixol 2-3 h before the posttreatment study with PET. The other two subjects received 0.5 mg orally three times during the 24 h preceding the posttreatment PET study, with the last dose being a dministered less than or equal to 4 h before the scan. All five ritans erin-treated subjects followed the same dosing regimen. During the 5 d ays preceding the posttreatment PET study, they were given a IO-mg tab let of ritanserin in the evening. The last dose was administered 2-1/2 hours before the study. Both flupenthixol and ritanserin pretreatment were associated with decreased binding of N-methyl-C-11-clozapine in dorsolateral and medial frontal cortical regions. These results suppor t previous findings that clozapine has. affinity for both dopamine D-1 and serotonin 5-HT2 receptors in the human frontal cortex. No consist ent change of binding was observed in striatal regions following flupe nthixol or ritanserin pretreatment. The clinical aspects of this featu re are discussed, both with respect to efficacy and side effects.