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.
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 the 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, 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Invernizzi
R
R
Istituto di Ricerche Farmacologiche, Mario Negri, Milan, Italy.
Fracasso
C
C
Caccia
S
S
Di Clemente
A
A
Garattini
S
S
Samanin
R
R
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003545:Cysteine / Q000494:pharmacology*; D005277:Fenfluramine / Q000494:pharmacology*; D007211:Indoles / Q000378:metabolism*; D008297:Male; D051381:Rats; D013997:Time Factors; D010133:p-Chloroamphetamine / Q000494:pharmacology*
D000662:Amphetamines; D007211:Indoles; D005277:Fenfluramine; D010133:p-Chloroamphetamine; D003545:Cysteine