5-HT2A receptor blockade in patients with schizophrenia treated with risperidone or clozapine. A SPET study using the novel 5-HT2A ligand 123I-5-I-R-91150

• Published in: British journal of psychiatry 1998-09, Vol.173 (3), p.236
• Main Authors: Travis, MJ, Busatto, GF, Pilowsky, LS, Mulligan, R, Acton, PD, Gacinovic, S, Mertens, J, Terriere, D, Costa, DC, Ell, PJ, Kerwin, RW
• Format: Article
• Language: English
• Subjects: Adult; Basal Ganglia Diseases - chemically induced; Basal Ganglia Diseases - metabolism; Clozapine - metabolism; Clozapine - therapeutic use; Female; Humans; Iodine Radioisotopes; Male; Piperidines; Receptors, Serotonin - metabolism; Risperidone - metabolism; Risperidone - therapeutic use; Schizophrenia - diagnostic imaging; Schizophrenia - drug therapy; Schizophrenia - metabolism; Serotonin Antagonists - metabolism; Serotonin Antagonists - therapeutic use; Tomography, Emission-Computed, Single-Photon
• ISSN: 0007-1250; 1472-1465
• DOI: 10.1192/bjp.173.3.236

5-HT2A receptor antagonism may be crucial to the action of atypical antipsychotics. Previous work has related 5-HT2A receptor blockade to clinical efficacy and protection from extrapyramidal side-effects. We developed a SPET imaging protocol for assessing 5-HT2A receptor binding using the selective ligand 123I-5-I-R91150. Six healthy volunteers, five clozapine- and five risperidone-treated subjects with DSM-IV schizophrenia were studied. Multi-slice SPET was performed on each subject. Cortex:cerebellum ratios were significantly lower in both clozapine- and risperidone-treated subjects compared with the healthy volunteers in all cortical regions. There was no difference in occupancy between the two drug-treated groups. No correlation was found between the percentage change in the Global Assessment Scale (GAS) and 5-HT2A receptor binding indices in the drug-treated groups. Clozapine and risperidone potently block 5-HT2A receptors in vivo. The lack of relationship between receptor binding indices and change in GAS suggests that 5-HT2A receptor blockade may be unrelated to clinical improvement. Future studies will substantiate this finding by studying 5-HT2A receptor binding in large groups of patients treated with both typical and novel atypical antipsychotics.