Effect of triamterene on 5-hydroxytryptamine biosynthesis in different brain areas.
Triamterene is structurally similar to the natural cofactor of tryptophan hydroxylase, (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin. The hydroxylation of tryptophan has been studied by measuring the accumulation of 5-hydroxytryptophan (5-HTP) and the concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in brainstem, frontal cortex and hypothalamus after inhibition of L-amino acid decarboxylase with benserazide hydrochloride and administration of either the vehicle or triamterene. Triamterene (30 mg/kg i.p.) decreased 5-HTP accumulation and 5-HT concentrations in brainstem and hypothalamus after 90 min; when the diuretic was given p.o. either acutely or chronically (triamterene 30 mg/kg twice daily during 4 days), no effect either on 5-HTP accumulation or on 5-HT and 5-HIAA concentrations was observed in the three brain areas studied. These results are in accordance with the 4 to 5 times higher concentrations of triamterene plus metabolites found in brainstem and hypothalamus after the acute i.p. administration of the drug than after an acute or chronic p.o. treatment. Hence, the effect of triamterene on 5-HT biosynthesis depends on the concentration it reaches in each brain area after i.p. or p.o. administration.
Steinberg
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P
García Bonelli
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Carlos Rubio
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M
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D001933:Brain Stem / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000096:biosynthesis*; D014223:Triamterene / Q000378:metabolism / Q000494:pharmacology*
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006916:5-Hydroxytryptophan; D014223:Triamterene