title: Striatal and extrastriatal dopamine D₂ receptor occupancy by the partial agonist antipsychotic drug aripiprazole in the human brain: a positron emission tomography study with [¹¹C]raclopride and [¹¹C]FLB457.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Clinical Neuroimaging Team, Molecular Neuroimaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Takahata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Harumasa
authors.initials: H
authors.lastname: Takano
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Arakawa
authors.forename: Hironobu
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kimura
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Kodaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nogami
authors.forename: Masayuki
authors.initials: M
authors.lastname: Suzuki
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Nagashima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimada
authors.forename: Motoichiro
authors.initials: M
authors.lastname: Kato
authors.forename: Masaru
authors.initials: M
authors.lastname: Mimura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism*; D000068180:Aripiprazole; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008297:Male; D010879:Piperazines / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D011759:Pyrrolidines / Q000378:metabolism; D015363:Quinolones / Q000378:metabolism*; D020891:Raclopride / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides / Q000378:metabolism; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D002250:Carbon Radioisotopes; D010879:Piperazines; D011759:Pyrrolidines; D015363:Quinolones; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C065065:FLB 457; D020891:Raclopride; D000068180:Aripiprazole