title: Effects of dopamine D2 receptor partial agonist antipsychotic aripiprazole on dopamine synthesis in human brain measured by PET with L-[β-11C]DOPA.
abstract: Dopamine D(2) receptor partial agonist antipsychotic drugs can modulate dopaminergic neurotransmission as functional agonists or functional antagonists. The effects of antipsychotics on presynaptic dopaminergic functions, such as dopamine synthesis capacity, might also be related to their therapeutic efficacy. Positron emission tomography (PET) was used to examine the effects of the partial agonist antipsychotic drug aripiprazole on presynaptic dopamine synthesis in relation to dopamine D(2) receptor occupancy and the resulting changes in dopamine synthesis capacity in healthy men. On separate days, PET studies with [(11)C]raclopride and L-[β-(11)C]DOPA were performed under resting condition and with single doses of aripiprazole given orally. Occupancy of dopamine D(2) receptors corresponded to the doses of aripiprazole, but the changes in dopamine synthesis capacity were not significant, nor was the relation between dopamine D(2) receptor occupancy and these changes. A significant negative correlation was observed between baseline dopamine synthesis capacity and changes in dopamine synthesis capacity by aripiprazole, indicating that this antipsychotic appears to stabilize dopamine synthesis capacity. The therapeutic effects of aripiprazole in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan. hito@nirs.go.jp
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: Hidehiko
authors.initials: H
authors.lastname: Takahashi
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Kodaka
authors.forename: Keisuke
authors.initials: K
authors.lastname: Takahata
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nogami
authors.forename: Masayuki
authors.initials: M
authors.lastname: Suzuki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D001667:Binding, Competitive; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000096:biosynthesis*; D065127:Dopamine D2 Receptor Antagonists; D006801:Humans; D007980:Levodopa / Q000493:pharmacokinetics; D008297:Male; D059906:Neuroimaging; D010879:Piperazines / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism*; D015363:Quinolones / Q000494:pharmacology*; D020891:Raclopride / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D002250:Carbon Radioisotopes; D065127:Dopamine D2 Receptor Antagonists; D010879:Piperazines; D015363:Quinolones; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D020891:Raclopride; D007980:Levodopa; D000068180:Aripiprazole; D004298:Dopamine