Ethyl (3-hydroxy-1-methylbutyl) barbituric acids as metabolites of pentobarbital.
نویسندگان
چکیده
Despite abundant pharmacological research on the 5,5-dialkylbarbituric acids, their metabolic fate has not been elucidated. Earlier studies (2, 3) from this laboratory proved that pentobarbital and Amytal are not detoxified by simple hydrolysis of the barbituric acid ring. The present report describes further experiments with isotopic pentobarbital which led to the isolation and characterization of two metabolites of the drug and their quantitative determination in the urine of dogs. After an anesthetic dose (50 mg. per kilo by mouth) of pentobarbital sodium labeled with N16, dogs excreted in the urine an average of 82 per cent of the administered isotope in the first 24 hours (2). Extraction of such urine at pH 6.5 with ether, ethyl acetate, or butanol removed 60 to 70 per cent of the excreted isotope; the remaining 30 to 40 per cent of the isotope could not be extracted at pH 6.5 with any common solvent. The metabolites discussed below, isolated from similar extracts of urine after ordinary, unlabeled pentobarbital, were separated and purified by means of their different solubilities in water. Both metabolites had an elementary composition corresponding to pentobarbital with 1 additional oxygen atom. They had the characteristic ultraviolet absorption spectrum of 5,5dialkylbarbituric acids. The presence of a hydroxyl group in each compound was indicated by an absorption band at 2.8 p in the infrared spectrum (Fig. 1) and proved by the preparation of crystalline acetates. Positive iodoform reactions demonstrated that both metabolites contained the CH&HOH group. Finally, treatment of each compound with concentrated sulfuric acid yielded ethylbarbituric acid;’ this reaction proved conclusively that in each case the hydroxyl group was located on the lmethylbutyl group and not on the ethyl group.
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ورودعنوان ژورنال:
- The Journal of biological chemistry
دوره 195 1 شماره
صفحات -
تاریخ انتشار 1952