Biotransformation of a new pyrrolidinone cognition-enhancing agent: isolation and identification of metabolites in human urine.
1. The metabolites of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide (DMPPA; MH-1), in the urine of human volunteers have been investigated. 2. Ten metabolites together with the unchanged drug (MH-1) were isolated by h.p.l.c. and identified by n.m.r. and mass spectrometry as: three metabolites hydroxylated in the pyrrolidine ring of MH-1 (MH-2, MH-3 and MH-4), three metabolites hydroxylated in the dimethylphenyl ring of MH-1 (MH-6, MH-7 and MH-8), N-[(2,6-dimethylphenylcarbamoyl)methyl]-4-hydroxybutyrylamide++ + (MH-5), N-[(2,6-dimethylphenyl-carbamoyl)methyl]succinamic acid (MH-9), the 3-O-sulphate of MH-6 (MH-10) and the 3-O-sulphate of N-(2,6-dimethyl-3-hydroxyphenyl)-2-(5-hydroxy-2-oxo-1-pyrrolidinyl)aceta mide (MH-11). 3. DMPPA was extensively metabolized. The principal metabolic transformations were hydroxylation of the pyrrolidine ring at the C5 carbon followed by oxidative C-N cleavage, and hydroxylation of the phenyl ring followed by sulphate conjugation.
Fujimaki
Y
Y
Drug Metabolism and Analytical Chemistry Research Center, Daiichi Pharmaceutical Co., Ltd., Japan.
Hashimoto
K
K
Sudo
K
K
Tachizawa
H
H
D001711:Biotransformation; D002491:Central Nervous System Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006900:Hydroxylation; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011760:Pyrrolidinones / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine
D002491:Central Nervous System Agents; D011760:Pyrrolidinones; C058876:nefiracetam