1. The interaction of some kynurenine pathway metabolites with 5-hydroxytryptophan and 5-hydroxytryptamine.
- Author
-
Handley SL and Miskin RC
- Subjects
- Animals, Dose-Response Relationship, Drug, Drug Interactions, Guinea Pigs, Hydroxylation, In Vitro Techniques, Kynurenine metabolism, Male, Mice, Movement drug effects, Muscle Contraction drug effects, Muscle, Smooth drug effects, Xanthurenates pharmacology, 5-Hydroxytryptophan pharmacology, Kynurenine pharmacology, Serotonin pharmacology
- Abstract
The kynurenine pathway metabolites kynurenine, 3-hydroxykynurenine and xanthurenic acid have been tested against 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP)-induced head twitches in the mouse in a dose-range of 0.5--5.0 mg/kg. Kynurenine and 3-hydroxykynurenine were highly active. Low doses caused marked potentiation of the twitch response to both 5-HT and 5-HTP with increased toxicity of 5-HT. High doses caused antagonism of both responses. Xanthurenic acid was inactive over the same dose range. The effects of kynurenine could not be duplicated in the guinea-pig ileum. The relevance of these results to the involvement of kynurenine pathway metabolites in depressive illness is discussed.
- Published
- 1977
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