5-HT2A RECEPTOR BLOCKADE IN PATIENTS WITH SCHIZOPHRENIA TREATED WITH RISPERIDONE OR CLOZAPINE - A SPET STUDY USING THE NOVEL 5-HT2A LIGAND I-123 5-I-R-91150

Background 5-HT2A receptor antagonism may be crucial to the action of atypical antipsychotics. Previous work has related 5-HT2A receptor blo ckade to clinical efficacy and protection from extrapyramidal side-eff ects. Method We developed a SPET imaging protocol for assessing 5-HT2A receptor binding using the selective ligand I-123-5-I-R91150. Six hea lthy volunteers, five clozapine- and five risperidone-treated subjects with DSM - IV schizophrenia were studied. Multi-slice SPET was perfor med on each subject. Results Cortex:cerebellum ratios were significant ly lower in both clozapine- and risperidone-treated subjects compared with the healthy volunteers in all cortical regions. There was no diff erence in occupancy between the two drug-treated groups. No correlatio n was found between-the percentage change in the Global Assessment Sca le (GAS) and 5-HT2A receptor binding indices in the drug-treated group s. Conclusions Clozapine and risperidone potently block 5-HT2A recepto rs in vivo. The lack of relationship between receptor binding indices and change in GAS suggests that 5-HT2A receptor blockade may be unrela ted to clinical improvement. Future studies will substantiate this fin ding by studying 5-HT2A receptor binding in large groups of patients t reated with both typical and novel atypical antipsychotics.