title: The antipsychotic sultopride is overdosed--a PET study of drug-induced receptor occupancy in comparison with sulpiride.
abstract: Conventional antipsychotics tend to elicit extrapyramidal symptoms at clinical doses, but dose optimization could reduce the risk of such side-effects. In-vivo receptor-binding studies have suggested that 70-80% of dopamine D2 receptor occupancy provides the desired antipsychotic effects without extrapyramidal symptoms. In terms of dose optimization based on the occupancy, there has not been enough supporting data regarding the clinical doses of the respective antipsychotics. In this study, we measured dopamine D2 receptor occupancy of two conventional benzamide antipsychotics, sulpiride and sultopride, using positron emission tomography, to investigate the rationale of their clinical dose. Although they are prescribed at similar doses (300-1200 mg), the doses required to obtain similar receptor occupancy (70-80%) were quite different: 1010-1730 mg for sulpiride but 20-35 mg for sultopride. In terms of dose, sultopride has about 50 times greater potency than sulpiride based on dopamine D2 receptor occupancy. Evidence for the optimal doses of conventional antipsychotics based on dopamine D2 receptor occupancy would be helpful for rational antipsychotic therapy.
authors.affiliation: Brain Imaging Project, National Institute of Radiological Sciences, 9-1, Anagawa 4-Chome, Inage-ku, Chiba, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takano
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Yasuno
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Takahashi
authors.forename: Takuya
authors.initials: T
authors.lastname: Morimoto
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kusuhara
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Okubo
mesh_terms: D000328:Adult; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D011869:Radioligand Assay / Q000379:methods; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D013469:Sulpiride; D000077582:Amisulpride