The distribution and metabolism of chlorpromazine in rats and the relationship to effects on cerebral monoamine metabolism

Eur J Pharmacol. 1976 Dec;40(2):263-72. doi: 10.1016/0014-2999(76)90061-3.

Abstract

Rats were injected with chlorpromazine (CPZ), 21 mumoles/kg (7.5 mg/kg) i.p., and killed after different time intervals up to 24 h. Mass fragmentographic methods were used to determine the levels of CPZ, monodemethyl-chlorpromazine (nor1-CPZ) and 7-hydroxy-chlorpromazine (7-OH-CPZ) in brain and blood and dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxy-3-indoleacetic acid (5-HIAA) in the striatum. Significant correlations between the brain and blood concentrations of CPZ as well as its active metabolites and the levels of DOPAC and HVA were obtained at several time points. The similarity between the time curves for CPZ dominantly the unchanged drug in the brain which determines the acceleration of DA metabolism.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Biogenic Amines / metabolism*
  • Brain / drug effects
  • Brain / metabolism*
  • Chlorpromazine / analogs & derivatives
  • Chlorpromazine / blood
  • Chlorpromazine / metabolism*
  • Corpus Striatum / metabolism
  • Homovanillic Acid / metabolism
  • Hydroxyindoleacetic Acid / metabolism
  • In Vitro Techniques
  • Male
  • Rats
  • Time Factors

Substances

  • Biogenic Amines
  • 3,4-Dihydroxyphenylacetic Acid
  • Hydroxyindoleacetic Acid
  • Chlorpromazine
  • Homovanillic Acid