Studies on the Metabolic N-Demethylation. II. Barbiturates Induced Acceleration of N-Methylbarbiturates Metabolism.

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The metabolism of hexobarbital, methylbarbital and methylphenobarbital was investigated from the viewpoint of demethylation using the liver slice of rats pretreated with barbiturates such as phenobarbital, methylbarbital and barbital. phenobarpital had the strongest effect in accelerating the metabolism of all substrates. Methylbarbital and methylphenobarbital, both which possess the C-5 side group stable to oxidation, were led by the pretreatment to the pathway of demethylation rather than to that of oxidation of C-5 substituted group. Although the oxidation of cyclohexenyl group in the metabolism of hexobarbital was stimulated by the pretreatment, no demethylated metabolite could be detected. When the cyclohexenyl group of substrate was oxidized beforehand, demethylation could take place and was promoted by the pretreatment. Based on these findings, the relationship between hydroxylation and demethylation of N-methylbarbiturates was discussed.

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