Effect of L-cysteine on the long-term depletion of brain indoles caused by p-chloroamphetamine and d-fenfluramine in rats Relation to brain drug concentrations

Roberto Invernizzi, Claudia Fracasso, Silvio Caccia, Angelo Di Clemente, Silvio Garattini, Rosario Samanin

Research output: Contribution to journalArticle

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Abstract

The effect of L-cysteine on the depletion of serotonin and 5-hydroxyindoleacetic acid concentrations caused by p-chloroamphetamine and d-fenfluramine was studied in various brain regions one week after drug injection. p-Chloroamphetamine (2.5 and 5 mg/kg i.p.) and d-fenfluramine (13.4 mg/kg i.p.) significantly reduced serotonin and 5-hydroxyindoleacetic acid levels in the striatum, hippocampus and cortex, particularly in the latter areas. L-cysteine (500 mg/kg i.p.), administered 30 min before and 5 h after p-chloroamphetamine or d-fenfluramine, significantly reduced the effect of either drug on the concentrations of both indoles without causing any effect by itself. In another experiment, the rats were treated as above and were killed at various times after p-chloroamphetamine or d-fenfluramine injection to determine, in parallel, the indole levels in the whole brain and concentration of p-chloroamphetamine, d-fenfluramine and its metabolite d-norfenfluramine in the plasma and brain. p-Chloroamphetamine and d-fenfluramine markedly lowered both indoles, particularly 16 and 24 h after injection. L-cysteine had no effect on the indole concentrations but significantly reduced the effect of p-chloroamphetamine and d-fenfluramine 16 and 24 h after injection. At these times, the brain concentrations of p-chloroamphetamine, d-fenfluramine and d-norfenfluramine were markedly lower in the L-cysteine-treated than in the control rats. Analysis of the blood concentration of p-chloroamphetamine, d-fenfluramine and d-norfenfluramine showed that the rats treated with L-cysteine eliminated the drugs studied more rapidly than the control animals. The results show that L-cysteine partially prevents the depletion of the brain content of serotonin and 5-hydroxyindoleacetic acid caused by p-chloroamphetamine and d-fenfluramine one week after drug administration. The fact that the effect of p-chloroamphetamine and d-fenfluramine seen at shorter times was associated with a marked reduction in the blood and brain drug concentration in the L-cysteine-treated animals suggests that the reduced availability of p-chloroamphetamine, d-fenfluramine and its active metabolite may be responsible for the partial prevention by L-cysteine of their neurochemical effects.

Original languageEnglish
Pages (from-to)77-83
Number of pages7
JournalEuropean Journal of Pharmacology
Volume163
Issue number1
DOIs
Publication statusPublished - Apr 12 1989

Fingerprint

p-Chloroamphetamine
Fenfluramine
Indoles
Cysteine
Brain
Pharmaceutical Preparations
Norfenfluramine
Hydroxyindoleacetic Acid
Serotonin
Injections

Keywords

  • d-Fenfluramine
  • d-Norfenfluramine
  • L-Cysteine
  • Neurotoxicity
  • p-Chloroamphetamine
  • Serotonin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Effect of L-cysteine on the long-term depletion of brain indoles caused by p-chloroamphetamine and d-fenfluramine in rats Relation to brain drug concentrations. / Invernizzi, Roberto; Fracasso, Claudia; Caccia, Silvio; Di Clemente, Angelo; Garattini, Silvio; Samanin, Rosario.

In: European Journal of Pharmacology, Vol. 163, No. 1, 12.04.1989, p. 77-83.

Research output: Contribution to journalArticle

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