TY - JOUR T1 - URINARY METABOLITES OF N-METHYL-α-METHYL-α-PHENYLSUCCINIMIDE (METHSUXIMIDE) IN THE DOG JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 113 LP - 122 VL - 2 IS - 2 AU - KENNETH H. DUDLEY AU - DANIEL L. BIUS AU - C. DANNY WALDROP Y1 - 1974/03/01 UR - http://dmd.aspetjournals.org/content/2/2/113.abstract N2 - After oral administration of N-methyl-α-methyl-α-phenylsuccinimide (methsuximide) to dogs, the apparent principal metabolites isolated from 48-hr urine were α-(p-hydroxyphenyl)-α-methylsuccinimide and N-methyl-α-(p-hydroxyphenyl)-α-methylsuccinimide. These materials were present in urine largely as conjugation products, their isolations being possible after release from their conjugated state by incubation of urine with β-glucuronidase (Helix pomatia) or by treatment of urine with mineral acid. In experiments in which dogs received oral doses of 1.0 or 2.0 g of methsuximide, the total 48-hr urinary yield of these para-hydroxylation products, as determined by gas chromatographic analysis of β-glucuronidase-treated urine samples, was roughly 7-20%. α-(p-Hydroxyphenyl)-α-methylsuccinimide was the major para-hydroxylation product isolated from urine. Only small amounts of the N-demethylated drug, α-methyl-α-phenylsuccinimide, were found, the urinary yields being of the same order as those whenα -methyl-α-phenylsuccinimide itself was administered to dogs. The N-demethylation reaction is probably primary. No unchanged methsuximide was found in 48-hr urine. In the present study the synthesis of 2-methyl-2-phenylsuccinamic acid and of 3-methyl-3-phenylsuccinamic acid allowed a systematic search for these potential ring-opened urinary products. There was no evidence that either isomer was present. It was demonstrated that the 3,3-isomer was not present and that the 2,2-isomer could not have been present in more than 0.2-0.3% yield of dose. Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics ER -