The interaction of some kynurenine pathway metabolites with 5-hydroxytryptophan and 5-hydroxytryptamine.
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.
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D006900:Hydroxylation; D066298:In Vitro Techniques; D007737:Kynurenine / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009068:Movement / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D014977:Xanthurenates / Q000494:pharmacology
D014977:Xanthurenates; D012701:Serotonin; D007737:Kynurenine; D006916:5-Hydroxytryptophan