Journal article
Striatal and extrastriatal D2/D3-receptor-binding properties of ziprasidone: a positron emission tomography study with [18F]Fallypride and [11C]raclopride (D2/D3-receptor occupancy of ziprasidone)
Journal of clinical psychopharmacology, Vol.28(6), pp.608-617
12/2008
DOI: 10.1097/JCP.0b013e31818ba2f6
PMID: 19011428
Abstract
To elucidate the "atypicality" of ziprasidone, its striatal and extrastriatal D2/D3-receptor binding was characterized in patients with schizophrenia under steady-state conditions. These data were compared with striatal receptor occupancy values after single-dose ziprasidone ingestion in healthy controls. [F]fallypride positron emission tomography (PET) recordings were obtained in 15 patients under steady-state ziprasidone treatment at varying time points after the last dose. Binding potentials were calculated for striatal and extrastriatal regions. D2/D3-receptor occupancies were expressed relative to binding potentials in 8 unmedicated patients. In a parallel [C]raclopride-PET study, striatal D2/D3-receptor occupancy was measured in healthy subjects after single oral doses of 40 mg ziprasidone or 7.5 mg haloperidol. Ziprasidone plasma concentrations correlated significantly with D2/D3-receptor occupancies in all volumes of interests. Occupancy in extrastriatal regions was approximately 10% higher than in striatal regions. Half maximal effective concentration values were consistently higher in striatal than in extrastriatal regions (temporal cortex: 39 ng/mL; putamen: 64 ng/mL), irrespective of the time between last dosing and scan. Single ziprasidone doses resulted in higher occupancies exceeding the 95% prediction limits of the occupancy versus plasma concentrations for chronic dosing. Ziprasidone shares moderate preferential extrastriatal D2/D3-receptor binding with some other atypicals. D2/D3-receptor occupancy is rapidly attuning to the daily course of ziprasidone plasma levels, suggesting relatively high intraday variations of D2/D3-receptor binding. The discrepancies between single-dose and steady-state results are important for the future design of dose-finding PET occupancy studies of novel antipsychotics. Single-dose studies may not be totally relied on for final dose selection.
Details
- Title: Subtitle
- Striatal and extrastriatal D2/D3-receptor-binding properties of ziprasidone: a positron emission tomography study with [18F]Fallypride and [11C]raclopride (D2/D3-receptor occupancy of ziprasidone)
- Creators
- Ingo Vernaleken - Department of Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, Germany. ivernaleken@ukaachen.deChristine FellowsHildegard JanouschekAnno BröchelerTanja VeselinovicChristian LandvogtChristian BoyHans-Georg BuchholzKatja SpreckelmeyerPeter BartensteinPaul CummingChristoph HiemkeFrank RöschWolfgang SchäferDean F WongGerhard Gründer
- Resource Type
- Journal article
- Publication Details
- Journal of clinical psychopharmacology, Vol.28(6), pp.608-617
- DOI
- 10.1097/JCP.0b013e31818ba2f6
- PMID
- 19011428
- NLM abbreviation
- J Clin Psychopharmacol
- ISSN
- 0271-0749
- eISSN
- 1533-712X
- Publisher
- United States
- Grant note
- K24 DA000412-09 / NIDA NIH HHS K24 DA000412 / NIDA NIH HHS K24 DA00412 / NIDA NIH HHS
- Language
- English
- Date published
- 12/2008
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984003981402771
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