Striatal and temporal cortical D2/D3 receptor occupancy by olanzapine and sertindole in vivo: a [I-123]epidepride single photon emission tomography (SPET) study

Rationale: Previous work suggests clozapine preferentially targets limbic c ortical dopamine systems, which could help account for its lack of extrapyr amidal side effects (EPS) and superior therapeutic efficacy. Objectives: To test the hypothesis that olanzapine, a novel atypical antipsychotic drug, occupies temporal cortical D3/D3 receptors to a greater extent than striata l D2/D3 receptors in vivo. Methods: Nine schizophrenic patients taking eith er olanzapine [(n=5: mean (SD) age: 32.5 (6.5) years; daily dose: 18.3 (2.6 ) mg)] or sertindole [(n=4: mean (SD) age: 30.3 (7.4) years; daily dose: 16 (5.6) mg] were studied with [I-123]epidepride (S)-N-[(1-ethyl- 2-pyrrolidi nyl)methyl]-5-iodo-2,3-dimethoxy-benzamide) and single photon emission tomo graphy (SPET). An estimate of [I-123]epidepride 'specific binding' to D2/D3 receptors was obtained in patients and age-matched healthy volunteers. A s ummary measure was generated representing striatal and temporal cortical re lative %D3/D3 receptor occupancy by antipsychotic drugs. Occupancy data wer e compared with previously studied groups of patients receiving typical ant ipsychotic drugs (n=12) and clozapine (n=10). Results: Mean striatal and te mporal cortical %D2/D3 receptor occupancy in olanzapine-treated patients wa s 41.3% (SD 17.9) and 82.8% (SD 4.2), respectively. Unexpectedly low levels of striatal relative %D2/D3 receptor occupancy were seen in two patients w ith typical antipsychotic-drug-induced movement disorder prior to switching to olanzapine. In the temporal cortex, mean D2/D3 dopamine receptor occupa ncy levels above 80% were seen for all antipsychotic drugs studied. Conclus ions: The atypical antipsychotic drugs olanzapine and sertindole, in common with clozapine, demonstrate higher occupancy of temporal cortical than str iatal D2/D3 dopamine receptors in vivo at clinically useful doses. This cou ld help mediate their atypical clinical profile of therapeutic efficacy wit h few extrapyramidal side effects. Limbic selective blockade of D2/D3 dopam ine receptors could be a common action of atypical antipsychotic drugs.