In vivo effects on striatal dopamine D[sub 2] receptor binding by the novel atypical antipsychotic drug sertindole - a [sup 123] I IBZM single photon emission tomography (SPET) study.

Abstract The novel antipsychotic drug sertindole has an atypical pharmacological profile. We have estimated striatal D[sub 2] dopamine binding in schizophrenic patients treated with sertindole using [sup 123]I iodobenzamide (IBZM) SPET Patients were recruited from a clinical trial of sertindole's tolerability and efficacy. Striatal D[sub 2] binding in sertindole-treated patients (n = 5), was compared with previously reported data from clozapine (n = 10); olanzapine (n = 6); typical antipsychotic responsive (n = 10); and risperidone (n = 6)-treated groups. Mean PANSS (structured clinical interview for the positive and negative syndrome scale) scores showed clinical improvement in the sertindole group. Few extrapyramidal side effects (EPS) were recorded [average Simpson-Angus (SAS) score = 2.6]. Sertindole-treated patients had mean D[sub 2] binding indices (+/- SE) significantly lower than clozapine-treated patients (1.19 +/- 0.04) versus (1.49 +/- 0.04), and olanzapine-treated patients (1.41 +/- 0.06); and similar to those of risperidone (1.24 +/- 0.04) and typical antipsychotic responsive (1.25 +/- 0.05) treated patients. In this patient sample the preliminary evidence suggests that sertindole's decreased tendency to induce EPS at clinically therapeutic doses is not due to limited occupancy of striatal D[sub 2] receptors in vivo, and as is the case for risperidone, patients are protected from EPS by some other intrinsic effect of the drug. [ABSTRACT FROM AUTHOR]