The time course of binding to striatal dopamine D-2 receptors by the neuroleptic ziprasidone (CP-88,059-01) determined by positron emission tomography

Positron emission tomography (PET) and C-11-raclopiide were used to assess the time course of binding to central dopamine D-2 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 D-2 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.