N-Acetyl, 4-O-methyldopa, a major metabolite of L-4-O-methyldopa in man and rat
| Autor: | Leiv Gjessing, Daniel Deruaz, Pierre Mathieu, Jacques Greffe, Roger Guilluy |
|---|---|
| Rok vydání: | 1976 |
| Předmět: |
Adult
Male medicine.medical_specialty Transamination Metabolite Dopamine Biochemistry Excretion Levodopa chemistry.chemical_compound Isomerism Species Specificity In vivo Internal medicine medicine Animals Humans cardiovascular diseases Methyldopa Pyruvates Pharmacology chemistry.chemical_classification Homovanillic acid Acetylation Homovanillic Acid Rats Metabolic pathway Endocrinology chemistry Lactates Female medicine.drug |
| Zdroj: | Biochemical pharmacology. 25(5) |
| ISSN: | 0006-2952 |
| Popis: | N-Acetyl, 4-O-methyldopa was identified as a major urinary metabolite of L -4-O- methyldopa , both in man and in the rat. The urinary metabolites were examined in man after oral and in rat after intraperitoneal administration of L -4-O- methyldopa , L -3-O- methyldopa , L -dopa and N-acetyl, 4-O-methyldopa. 4-Mdopa was found to be converted mainly to N-acetyl, 4-Mdopa and iso-HVA and very little to the corresponding pyruvic and lactic acids, whereas 3-Mdopa was metabolized to its pyruvic, lactic and acetic (HVA) derivatives and practically not acetylated. It is suggested therefore that the 3-hydroxy,4-methoxy group (the iso-vanyl structure) prevents transamination and that N-acetylation represents an alternative metabolic pathway. The lack of N-acetyl,4-O-methyldopa after the L -dopa loads shows that L -dopa is not 4-O-methylated and therefore that 4-O-methyldopa is not, or only in a minute amount if any, an in vivo metabolite of L -dopa. N-Acetyl,4-Mdopa administration to rats resulted in excretion of the compound almost unchanged. These results agree with a previous suggestion by the authors of partly distinct metabolic routes for the O-methyl catecholamines according to whether the methyl group is bound on the meta or on the para position and raises the question as to what extent iso-HVA levels in body fluids are representative of a para-O-methylation of dopamine, implicated in neuropsychiatric disorders. |
| Databáze: | OpenAIRE |
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