Rationale: Second-generation antipsychotics demonstrate clinical efficacy with fewer extrapyramidal side effects compared with first-generation antipsychotics. One of the proposed explanations is the hypothesis of preferential extrastriatal dopamine D 2 receptor occupancy (limbic selectivity) by antipsychotics. In the present study, we focused on aripiprazole, which has a unique pharmacological profile with partial agonism at dopamine D 2 receptors and the minimal risk of extrapyramidal side effects. Previous positron emission tomography (PET) studies using high-affinity radioligands for dopamine D 2 receptors have reported inconsistent results regarding regional differences of dopamine D 2 receptor occupancy by aripiprazole. Objective: To test the hypothesis of preferential binding to extrastriatal dopamine D 2 receptors by aripiprazole, we investigated its regional dopamine D 2 receptor occupancies in healthy young subjects. Materials and methods: Using PET and two radioligands with different affinities for dopamine D 2 receptors, [ 11C] raclopride and [ 11C]FLB457, striatal and extrastriatal dopamine D 2 receptor bindings at baseline and after oral administration of 6 mg aripiprazole were measured in 11 male healthy subjects. Results: Our data showed that dopamine D 2 receptor occupancies in the striatum measured with [ 11C]raclopride were 70.1% and 74.1%, with the corresponding values for the extrastriatal regions measured with [ 11C]FLB457 ranging from 46.6% to 58.4%. Conclusions: In the present study, preferential extrastriatal dopamine D 2 receptor occupancy by aripiprazole was not observed. Our data suggest partial agonism at dopamine D 2 receptors is the most likely explanation for the minimal risk of extrapyramidal side effects in the treatment by aripiprazole.
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