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ALTERATIONS IN BRAIN 5‐HYDROXY‐TRYPTAMINE METABOLISM DURING THE ‘WITHDRAWAL’ PHASE AFTER CHRONIC TREATMENT WITH DIAZEPAM AND BROMAZEPAM
Author(s) -
AGARWAL R.A.,
LAPIERRE Y.D.,
RASTOGI R.B.,
SINGHAL R.L
Publication year - 1977
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1977.tb16740.x
Subject(s) - bromazepam , diazepam , endocrinology , medicine , benzodiazepine , chemistry , 5 hydroxyindoleacetic acid , monoamine oxidase , hypothalamus , striatum , serotonin , pharmacology , dopamine , receptor , biochemistry , enzyme
1 Daily administration of diazepam or bromazepam (10 mg/kg) for 22 days significantly increased the activity of mid‐brain tryptophan hydroxylase by 36% and 39%, respectively. The concentration of tryptophan was also enhanced in the mid‐brain region of rats subjected to benzodiazepine treatment. 2 Chronic therapy with either of the two anti‐anxiety agents enhanced the endogenous levels of 5‐hydroxytryptamine and 5‐hydroxyindoleacetic acid in cerebral cortex, hypothalamus, pons‐medulla, mid‐brain and striatum. 3 Whereas diazepam treatment decreased (13%) the activity of monoamine oxidase in mid‐brain, bromazepam failed to exert any effect, suggesting that the observed elevation in 5‐hydroxyindoleacetic acid levels is not associated with enhanced deamination of 5‐hydroxytryptamine. 4 Discontinuation of treatment for 48 h significantly decreased the activity of mid‐brain tryptophan hydroxylase to levels that were significantly lower than those seen for benzodiazepine‐treated and normal rats. The concentrations of mid‐brain tryptophan and 5‐hydroxytryptamine were also reduced in various brain regions examined. 5 Withdrawal from diazepam or bromazepam therapy further augmented the levels of brain 5‐hydroxyindoleacetic acid. 6 The results demonstrate that the depressant effects on behaviour of these agents are accompanied by increased metabolism of 5‐hydroxytryptamine in the brain. Withdrawal from these minor tranquillizers, on the other hand, reduces the synthesis of this indoleamine.