DOPAMINE D-2 RECEPTOR BLOCKADE IN-VIVO WITH THE NOVEL ANTIPSYCHOTICS RISPERIDONE AND REMOXIPRIDE - AN I-123 IBZM SINGLE-PHOTON EMISSION TOMOGRAPHY (SPET) STUDY

Risperidone and remoxipride are recently introduced atypical antipsychotics, with clinical efficacy comparable to that of classical antipsychotics but lower propensity to induce extrapyramidal side effects (EPS). It is unclear whether these properties relate to weak dopamine D-2 receptor blockade in vivo, as has been suggested for the archetypal atypical antipsychotic clozapine. We have used I-123-IBZM single photon emission tomography (SPET) to characterize the patterns of striatal D-2 receptor binding in vivo in DSMIII-R-diagnosed schizophrenic and schizo-affective patients treated with either risperidone (n = 6) or remoxipride (n = 4) but predominantly EPS free. These groups were compared to age- and BPRS- matched subjects from a previously reported D-2 receptor binding database of patients treated with clozapine (n = 10) and classical antipsychotics (n = 10). Patients on risperidone and remoxipride had high levels of D-2 receptor blockade, comparable to those of patients on classical antipsychotics, and significantly greater than those obtained with clozapine-treated patients (risperidone versus clozapine, P<0.005; remoxipride versus clozapine, P<0.025). These results suggest high levels of striatal D-2 receptor occupancy in association with remoxipride and risperidone treatment and argue against modest D-2 antagonism as the explanation for the low incidence of EPS associated with these drugs.