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.
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.
Using PET and two radioligands with different affinities for dopamine D-2 receptors, [C-11]raclopride and [C-11]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.
Our data showed that dopamine D-2 receptor occupancies in the striatum measured with [C-11]raclopride were 70.1% and 74.1%, with the corresponding values for the extrastriatal regions measured with [C-11]FLB457 ranging from 46.6% to 58.4%.
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.