Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Psychopharmacology, 2012-07, Vol.222 (1), p.165

Ort / Verlag

Heidelberg: Springer Nature B.V

Erscheinungsjahr

2012

Quelle

Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• 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^sub 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^sub 2^ receptors and the minimal risk of extrapyramidal side effects. Previous positron emission tomography (PET) studies using high-affinity radioligands for dopamine D^sub 2^ receptors have reported inconsistent results regarding regional differences of dopamine D^sub 2^ receptor occupancy by aripiprazole. To test the hypothesis of preferential binding to extrastriatal dopamine D^sub 2^ receptors by aripiprazole, we investigated its regional dopamine D^sub 2^ receptor occupancies in healthy young subjects. Using PET and two radioligands with different affinities for dopamine D^sub 2^ receptors, [^sup 11^C]raclopride and [^sup 11^C]FLB457, striatal and extrastriatal dopamine D^sub 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^sub 2^ receptor occupancies in the striatum measured with [^sup 11^C]raclopride were 70.1% and 74.1%, with the corresponding values for the extrastriatal regions measured with [^sup 11^C]FLB457 ranging from 46.6% to 58.4%. In the present study, preferential extrastriatal dopamine D^sub 2^ receptor occupancy by aripiprazole was not observed. Our data suggest partial agonism at dopamine D^sub 2^ receptors is the most likely explanation for the minimal risk of extrapyramidal side effects in the treatment by aripiprazole.[PUBLICATION ABSTRACT]