Striatal and extrastriatal dopamine D 2 receptor occupancy by the partial agonist antipsychotic drug aripiprazole in the human brain: A positron emission tomography study with [ 11C]raclopride and [ 11C]FLB457

Keisuke Takahata, Hiroshi Ito, Harumasa Takano, Ryosuke Arakawa, Hironobu Fujiwara, Yasuyuki Kimura, Fumitoshi Kodaka, Takeshi Sasaki, Tsuyoshi Nogami, Masayuki Suzuki, Tomohisa Nagashima, Hitoshi Shimada, Motoichiro Kato, Masaru Mimura, Tetsuya Suhara

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)165-172
Number of pages8
JournalPsychopharmacology
Volume222
Issue number1
DOIs
Publication statusPublished - 2012 Jul 1

Keywords

  • Antipsychotics
  • Aripiprazole
  • Dopamine D receptor
  • Occupancy
  • Partial agonist

ASJC Scopus subject areas

  • Pharmacology

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