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Effect of clozapine on the metabolism of serotonin in rat brain

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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 sleepinducing properties of this drug.

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Authors and Affiliations

  1. a Sandoz Research Unit, Research Institute Wander, Berne, Switzerland

    Walter Ruch, Helmuth Asper & Hans R. Bürki

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  1. Walter Ruch
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  2. Helmuth Asper
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  3. Hans R. Bürki
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Ruch, W., Asper, H. & Bürki, H.R. Effect of clozapine on the metabolism of serotonin in rat brain. Psychopharmacologia 46, 103–109 (1976). https://doi.org/10.1007/BF00421556

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  • DOI: https://doi.org/10.1007/BF00421556

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