Abstract. Olanzapine is a new atypical antipsychotic agent that belongs to the same chemical class as cloza- pine. The pharmacological efficacy of olanzapine (in 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 study were (a) to assess dopamine D 2 /D 3 receptor availability in patients treated with olanzapine by means of iodine-123 iodobenzamide [ 123 I]IBZM single-photon emission tomography (SPET), (b) to compare the results with findings of [ 123 I]IBZM SPET in patients under treatment with risperidone and (c) to correlate the results with the occurrance of extrapyramidal side-effects (EPMS). Brain SPET scans were performed in 20 schizophrenic patients (DSM III R) at 2 h after i.v. ad- ministration of 185 MBq [ 123 I]IBZM. Images were ac- quired using a triple-head gamma camera (Picker Prism 3000 XP). For semiquantitative evaluation of D 2 /D 3 re- ceptor binding, transverse slices corrected 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 binding was reduced in all patients treated with olanza- pine. Specific IBZM binding [STR–BKG]/BKG ranged from 0.13 to 0.61 (normal controls >0.95). The de- creased D 2 /D 3 receptor availability revealed an exponen- tial dose-response relationship (r=–0.85, P<0.001). The slope of the curve was similar to that of risperidone and considerably higher than that of clozapine as compared with the results of a previously published study. EPMS were observed in only one patient, presenting with the lowest D 2 /D 3 availability. The frequency of EPMS in- duced by olanzapine (5%) was considerably lower than the frequency under risperidone treatment (40%). Our findings suggest an exponential 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 affinity and a similar 5HT 2 recep- tor affinity of olanzapine as compared with clozapine. Thus, the decreased tendency to induce EPMS at thera- peutic doses is not due to the limited occupancy of stri- atal D 2 /D 3 receptors in vivo. Patients are protected from EPMS by other intrinsic effects of the drug, i.e. the com- bination of both D 2 /D 3 and 5HT 2 receptor antagonism. Key words: Iodine-123 iodobenzamide – Single-photon emission tomography – Schizophrenia – Olanzapine Eur J Nucl Med (1999) 26:862–868 Introduction The development of neuroleptic drugs has significantly enhanced the treatment of patients with schizophrenia. However, neuroleptics also produce a variety of auto- nomic nervous system side-effects and extrapyramidal symptoms (EPMS). The emergence of clozapine, a high- ly efficacious antipsychotic drug with a very low propen- sity for causing EPMS, has revitalized interest in under- standing the pharmacological basis of treatment for schizophrenia. Though clozapine treatment generally does not induce motor dysfunction, its infrequent associ- ation with reversible agranulocytosis has restricted its present use to schizophrenic patients who have failed to respond to traditional antipsychotic therapy [1]. There are continuing efforts to find other novel antipsychotic agents that are efficacious and have a low extrapyrami- dal symptom liability like clozapine, but with a superior safety margin. Original paper 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 Stefan Dresel 1 , Torsten Mager 2 , Bernd Rossmüller 1 , Eva Meisenzahl 2 , Klaus Hahn 1 , Hans-Jürgen Möller 2 , Klaus Tatsch 1 1 Department of Nuclear Medicine, University of Munich, Ziemssenstrasse 1, D-80336 Munich, Germany 2 Department of Psychiatry, University of Munich, Germany Received 6 March 1999 / in revised form 11 April 1999 European Journal of Nuclear Medicine Vol. 26, No. 8, August 1999 – ©Springer-Verlag 1999