201. Effect of clozapine on the metabolism of serotonin in rat brain.
- Author
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Ruch W, Asper H, and Bürki HR
- Subjects
- Animals, Brain metabolism, Brain Stem metabolism, Haloperidol pharmacology, Hydroxyindoleacetic Acid metabolism, Limbic System metabolism, Loxapine pharmacology, Male, Rats, Thioridazine pharmacology, Tryptophan analogs & derivatives, Tryptophan metabolism, Tryptophan Hydroxylase antagonists & inhibitors, Brain drug effects, Clozapine pharmacology, Dibenzazepines pharmacology, Serotonin metabolism
- Abstract
Clozapine, but not chlorpromazine, haloperidol, thioridazine, or loxapine, increases the concentrations of tryptophan, serotonin, and 5-hydroxyindoleacetic acid in the brain of the rat. This effect of clozapine is due to an increased serotonin synthesis as demonstrated by an enhanced accumulation of 3H-serotonin in the brain after i.v. infusion of 3H-tryptophan. Clozapine also elevates the plasma concentration of free tryptophan, and reduces the plasma concentration of total tryptophan. Therefore, clozapine may increase the brain serotonin concentration by enhancing the availability of tryptophan in the brain, thereby promoting serotonin synthesis. Measurement of the rate of disappearance from the brain of 3H-serotonin or of endogenous serotonin after synthesis inhibition with 6-fluorotryptophan shows that clozapine has no direct effect on the release and degradation of serotonin. The effect of clozapine on brain serotonergic systems may possibly be related to the pronounced sedative and sleep-inducing properties of this drug.
- Published
- 1976
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