PET MEASUREMENTS OF NEURORECEPTOR OCCUPANCY BY TYPICAL AND ATYPICAL NEUROLEPTICS

The goal of this study was to use PET and C-11-N-methylspiperone (C-11 -NMSP) to measure the differences in relative occupancy of serotonin ( 5-hydroxytryptamine-2 or 5-HT24) and dopamine-2 (D2) neuroreceptors in subjects being treated with typical or atypical antipsychotic drugs. Methods: We used PET and single-dose C-11-NMSP to measure receptor ind ices and relative receptor occupancy of 5-HT2A receptors in frontal co rtex and D2 receptors in basal ganglia in five subjects who were neuro leptic free, five subjects who were being treated with typical antipsy chotic drugs and five subjects who were being treated with clozapine, an atypical antipsychotic drug. Results: Among the three groups, there were significant differences in 5-HT2A indices, D2 indices and the ra tio of 5-HT2A to D2 indices. With no overlap, the 5-HT2A index separat ed all subjects who received clozapine and the D2 index separated the remaining two groups. Conclusion: Typical antipsychotic and atypical a ntipsychotic subjects do have differing patterns of 5-HT2A and D2 rela tive-receptor occupancy when measured with a single PET scan, single C -11-NMSP radiotracer dose and no separately injected ''cold'' pharmace utical.