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 D2 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 D2 receptors and the minimal risk of extrapyramidal side effects. Previous positron emission tomography (PET) studies using high-affinity radioligands for dopamine D2 receptors have reported inconsistent results regarding regional differences of dopamine D2 receptor occupancy by aripiprazole.
Objective
To test the hypothesis of preferential binding to extrastriatal dopamine D2 receptors by aripiprazole, we investigated its regional dopamine D2 receptor occupancies in healthy young subjects.
Materials and methods
Using PET and two radioligands with different affinities for dopamine D2 receptors, [11C]raclopride and [11C]FLB457, striatal and extrastriatal dopamine D2 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 D2 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 D2 receptor occupancy by aripiprazole was not observed. Our data suggest partial agonism at dopamine D2 receptors is the most likely explanation for the minimal risk of extrapyramidal side effects in the treatment by aripiprazole.