Biotransformation of a new pyrrolidinone cognition-enhancing agent: isolation and identification of metabolites in human urine

Xenobiotica. 1990 Oct;20(10):1081-94. doi: 10.3109/00498259009046828.

Abstract

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.

MeSH terms

  • Biotransformation
  • Central Nervous System Agents / chemistry
  • Central Nervous System Agents / pharmacokinetics
  • Central Nervous System Agents / urine
  • Chromatography, High Pressure Liquid
  • Humans
  • Hydroxylation
  • Magnetic Resonance Spectroscopy
  • Male
  • Molecular Structure
  • Oxidation-Reduction
  • Pyrrolidinones / chemistry
  • Pyrrolidinones / pharmacokinetics*
  • Pyrrolidinones / urine

Substances

  • Central Nervous System Agents
  • Pyrrolidinones
  • nefiracetam