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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Low striatal and extra-striatal D2 receptor occupancy during treatment with the atypical antipsychotic sertindole.

RATIONALE: Sertindole is a new atypical antipsychotic drug. Preclinical pharmacology suggests that sertindole has a preferential effect on the activity of limbic and cortical dopaminergic neurons. Clinical trials have shown antipsychotic efficacy and very few extrapyramidal symptoms (EPS) with sertindole at 20 mg/day. OBJECTIVES: This positron emission tomography (PET) study aimed to measure D(2) receptor occupancy in striatal and extra-striatal regions induced by clinically representative doses of sertindole in patients with schizophrenia. METHOD: Four stabilized schizophrenic out-patients received sertindole 20 mg/day for 6-8 weeks. PET was performed using [(11)C]raclopride to measure D(2) receptor occupancy in the striatum and [(11)C]FLB457 to measure occupancy in the neocortex and thalamus, i.e. regions with very low D(2) receptor density.RESULTS: Striatal D(2) receptor occupancy was 52-68%. Similar occupancies were found in the thalamus, and the temporal and frontal cortices. CONCLUSIONS: Sertindole appears efficacious at a low D(2) receptor occupancy, comparable to that produced by clozapine. This finding could explain the low risk of EPS. The functional limbic selectivity of sertindole was not reflected in regional differences in receptor occupancy.[1]


  1. Low striatal and extra-striatal D2 receptor occupancy during treatment with the atypical antipsychotic sertindole. Nyberg, S., Olsson, H., Nilsson, U., Maehlum, E., Halldin, C., Farde, L. Psychopharmacology (Berl.) (2002) [Pubmed]
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