title: The time course of binding to striatal dopamine D2 receptors by the neuroleptic ziprasidone (CP-88,059-01) determined by positron emission tomography.
abstract: Positron emission tomography (PET) and 11C-raclopride were used to assess the time course of binding to central dopamine D2 receptors by the novel neuroleptic ziprasidone. In a third party blind study, six healthy male control subjects received a predose of 40 mg ziprasidone and were scanned at an interval of between 4 and 36 h post-dose. One additional subject was assigned to placebo predose and was scanned at 4 h post-dose. Binding potential (BP) was compared with that seen in the subject predosed with placebo and with that seen in nine unmedicated normal volunteers. Subjects studied up to 12 h post-dose had BPs that were greater than 2 SD less than the mean BP, indicative of extensive D2 receptor binding by ziprasidone. With increasing time between dosing and PET scanning there was a curvilinear increase in BP, so that all studies performed at or after 18 h post-dose gave BPs in the normal range (mean +/- 2 SD). Elevated prolactin levels returned to within the normal range by 18 h post-dose. PET measures of binding potential correlated significantly with serum levels of ziprasidone at the time of scanning and less significantly with absolute prolactin levels at the same time.
authors.affiliation: MRC Cyclotron Unit, Hammersmith Hospital, London, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Bench
authors.forename: A A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: P M
authors.initials: PM
authors.lastname: Grasby
authors.forename: R J
authors.initials: RJ
authors.lastname: Dolan
authors.forename: S J
authors.initials: SJ
authors.lastname: Warrington
authors.forename: M
authors.initials: M
authors.lastname: Boyce
authors.forename: K P
authors.initials: KP
authors.lastname: Gunn
authors.forename: L Y
authors.initials: LY
authors.lastname: Brannick
authors.forename: R S
authors.initials: RS
authors.lastname: Frackowiak
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism* / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D008297:Male; D010879:Piperazines / Q000378:metabolism* / Q000493:pharmacokinetics; D011388:Prolactin / Q000097:blood; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012457:Salicylamides; D013844:Thiazoles / Q000378:metabolism* / Q000493:pharmacokinetics; D013997:Time Factors; D014055:Tomography, Emission-Computed
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D013844:Thiazoles; D020891:Raclopride; C092292:ziprasidone; D011388:Prolactin