Kinetics of piribedil and effects on dopamine metabolism: hepatic biotransformation is not a determinant of its dopaminergic action in rats

S. Sarati, G. Guiso, S. Garattini, S. Caccia

Research output: Contribution to journalArticlepeer-review

Abstract

The importance of hepatic metabolism in relation to the central (dopaminergic) effects of piribedil (PD) is still not really known. Plasma and brain kinetics and the effects on striatal dopamine (DA) metabolism of the parent drug and its known metabolites were therefore evaluated in rats, a species widely used in neurochemical studies of this drug. PD injected intraperitoneally (IP, 15-60 mg/kg) and centrally (ICV, 100-200 μg/rat) lowered striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylacetic acid (HVA) content and the intensity and time-course of the neurochemical effects were route- and dose-relatedly dependent on brain PD kinetics. The catechol (M1), p-hydroxylated (M2) and N-oxide (M3) metabolites of the drug were detectable only in trace amounts in rat brain and only at the highest IP dose tested; when administered ICV at doses equimolar to PD they caused no decrease in striatal DA metabolites, although striatal concentrations were higher than after IP PD, being comparable to or higher than those of the ICV parent drug. These data suggest that metabolites do not contribute to the dopaminergic effects of PD in rats.

Original languageEnglish
Pages (from-to)541-545
Number of pages5
JournalPsychopharmacology
Volume105
Issue number4
DOIs
Publication statusPublished - Dec 1991

Keywords

  • Dopaminergic system
  • Kinetics
  • Metabolism
  • Piribedil
  • Rat

ASJC Scopus subject areas

  • Pharmacology

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