Distribution of fluphenazine and its metabolites in brain regions and other tissues of the rat

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
M AravagiriR J Baldessarini

Abstract

Rats were given 5, 10, or 20 mg/kg oral doses of fluphenazine (FLU) dihydrochloride daily for 15 days. FLU and its sulfoxide (FL-SO), 7-hydroxy (7-OH-FLU) and N4'-oxide (FLU-NO) metabolites were assayed in plasma, liver, kidney, fat, whole brain, and brain regions by specific and sensitive radioimmunoassays (RIA). All metabolites were detected in tissues at higher levels than in plasma, and the levels increased with dose. FLU was 10- to 27-fold higher in brain regions than in plasma. Brain vs plasma levels of FLU correlated more closely than levels of its metabolites. Liver contained the highest levels of all analytes at all doses. FLU-SO was the major metabolite in brain regions (24% to 96% of FLU) and accumulated in fat 43 to 75 times more than FLU. Levels of 7-OH-FLU and FLU-NO were very low in brain (1% to 20% of FLU). FLU-SO and FLU-NO had only 1% to 3% the affinity for D1 and D2 receptors, but 7-OH-FLU had 20% the D2 and 5% the D1 affinity of FLU. The low affinity for dopamine receptors and low brain-levels of metabolites of FLU indicate that they are not likely to contribute importantly to pharmacologic responses of FLU. Also, the estimated relative "activity factor" for these compounds in the brain indicated that the co...Continue Reading

Citations

Jun 7, 2005·Forensic Science International : Synergy·Kabrena E RoddaOlaf H Drummer
Sep 16, 2010·Cancer Research·Xiaofeng XiaStephen T C Wong
Apr 4, 2002·Journal of Pharmaceutical and Biomedical Analysis·Claudia CimpoiuFlorin-Dan Irimie
Jul 11, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Helliner S VestriW Timothy Garvey
Jan 16, 2007·Biochemical and Biophysical Research Communications·Susanne ThümmlerMichel Lazdunski
Dec 20, 2014·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Pedro GonçalvesFátima Martel
Jun 28, 2000·Biopharmaceutics & Drug Disposition·M AravagiriS R Marder

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