Stereoselective Demethylation of the Enantiomers of Nefopam, an Experimental Antidepressant and Skeletal Muscle Relaxant

Abstract

Abstract1. Nefopam, an experimental skeletal muscle relaxant and antidepressant agent, was N-demethylated by the 9000 g supernatant fractions of human, rabbit and rat liver.2. Rates of demethylation of the optical isomers of nefopam differed in the three species examined, the (+)-isomer being demethylated faster than the (-)-isomer in each case.3. Kinetic analysis of the demethylation of nefopam isomers by rat liver indicated that both isomers were demethylated by the same enzyme system. In vivo studies in rabbit demonstrated stereoselective metabolism of the drug.4. More nornefopam was excreted following administration of (+)-nefopam than (-)-nefopam.