IODINE-123-IODOBENZAMIDE SPECT ASSESSMENT OF DOPAMINE D-2 RECEPTOR OCCUPANCY IN RISPERIDONE-TREATED SCHIZOPHRENIC-PATIENTS

The recently introduced neuroleptic, risperidone, was expected to bloc k fewer dopamine D-2 receptors than typical neuroleptics (e.g., halope ridol), but at comparable potency, The aim of this study was to evalua te the degree of dopamine D-2 receptor occupancy in relation to the ne uroleptic dosage and to correlate the findings with the presence of ex trapyramidal symptoms (EPS), Additionally the data were compared to pr evious iodobenzamide (IBZM) SPECT findings in patients treated with ot her neuroleptics, haloperidol and clozapine, Methods: In 20 patients w ith schizophrenia [Diagnostic and Statistical Manual of Mental Disorde rs (Third Edition-Revised)] treated with mean daily doses of risperido ne ranging from 0.029 to 0.128 mg/kg body weight, SPECT was performed 2 hr after intravenous injection of 185 MBq I-123-IBZM, a selective do pamine D-2 receptor ligand, Striatal IBZM binding was assessed by calc ulating a striatal/frontal cortex ratio, expressed as a percentage of the control value. Results: Selective dopamine D-2 receptor binding of the ligand was reduced in all treated patients, with binding values r anging from 7% to 68%. The degree of occupancy displayed an exponentia l dose-response relationship (r = -0.86; p < 0.0001). The slope of the curve was between those of haloperidol and clozapine but was closer a nd more similar in shape to the curve of haloperidol. Extrapyramidal s ymptoms were observed in 8 of 20 patients with binding values between 7% and 47%. However, there was no clear relationship between the degre e of receptor occupancy and the presence of EPS, Conclusion: The findi ngs suggest an exponential dose-response relationship between the dail y dosage of risperidone and the dopamine D-2 receptor occupancy. The b lockade of specific striatal IBZM binding found under therapy with ris peridone is between those of haloperidol and clozapine. The dose-respo nse curve for risperidone, however, shows greater similarity to that o f haloperidol.