In vivo effects of olanzapine on striatal dopamine D-2/D-3 receptor binding in schizophrenic patients: an iodine-123 iodobenzamide single-photon emission tomography study

Olanzapine is a new atypical antipsychotic agent that belongs to the same c hemical class as clozapine. The pharmacological efficacy of olanzapine tin contrast to that of risperidone) has been shown to be comparable to that of clozapine, but olanzapine has the advantage of producing a less pronounced bone marrow depressing effect than clozapine. The specific aims of this st udy were (a) to assess dopamine D-2/D-3 receptor availability in patients t reated with olanzapine by means of iodine-123 iodobenzamide [I-123]IBZM sin gle-photon emission tomography (SPET), (b) to compare the results with find ings of [I-123]IBZM SPET in patients under treatment with risperidone and ( c) to correlate the results with the occurrance of extrapyramidal side-effe cts (EPMS), Brain SPET scans were performed in 20 schizophrenic patients (D SM III R) at 2 h after i.v, administration of 185 MBq [I-123]IBZM. Images w ere acquired using a triple-head gamma camera (Picker Prism 3000 XP). For s emiquantitative evaluation of D-2/D-3 receptor binding, transverse slices c orrected for attenuation were used to calculate specific uptake values [STR -BKG]/BKG (STR=striatum; BKG=background). The mean daily dose of olanzapine ranged from 0.05 to 0.6 mg/kg body weight. The dopamine D-2/D-3 receptor b inding was reduced in all patients treated with olanzapine. Specific IBZM b inding [STR-BKG]/BKG ranged from 0.13 to 0.61 (normal controls >0.95). The decreased D2/D3 receptor availability revealed an exponential dose-response relationship (r=-0.85, P<0.001), The slope of the curve was similar to tha t of risperidone and considerably higher than that of clozapine as compared with the results of a previously published study. EPMS were observed in on ly one patient, presenting with the lowest D-2/D-3 availability. The freque ncy of EPMS induced by olanzapine (5%) was considerably lower than the freq uency under risperidone treatment (40%). Our findings suggest an exponentia l relationship between the daily dose of olanzapine striatal and decreased D-2/D-3 striatal binding availability. The results are consistent with the findings of in vitro experiments reporting a higher D-2/D-3 receptor affini ty and a similar 5HT(2) receptor affinity of olanzapine as compared with cl ozapine. Thus, the decreased tendency to induce EPMS at therapeutic doses i s not due to the limited occupancy of striatal D-2/D-3 receptors in vivo. P atients are protected from EPMS by other intrinsic effects of the drug, i.e . the combination of both D-2/D-3 and 5HT(2) receptor antagonism.