Deuterated (-)-verapamil, (28)-(-)-2-(2,5,6-β¬I3-3,4-dimethoxyphenyl)-2-2 2 isopropyl-5-[(2,5,6-H 3,4-dimethoxyphenethyl)methylamino]valeronitrile, and its analog (-)-H gallopamil. (2S)-(-)-2-(2,6-H2-3,4,5-trimethoxyphenyl)-2isopropyl-5-[ (2,s ,6-H3-3 ,4-dimethoxyphenethyl)methylamino]valeronitrile, were prepared. (-)-Gallopamil readily incorporated five atoms of deuterium into the 3-2 2 5-2 L available positions in the aromatic rings. ring trideuterated 3,4-dimethoxyphenylacetic acid and (2.9)-(+)-triphenylmethoxy-2-[(methanesulfonyl)oxy]propane. were incorporated into the aromatic ring of the ~-methyl-3,4-dimethoxyphenethylamine moiety incorporated as the the short E-alkyl side chain. l-13C-Methylverapamil was prepared from E-13C-methyl-3 ,4-dimethoxyphenethylamine. (-)-H6-Verapamil was prepared from Three additional atoms of deuterium INTRODUCTION Verapamil (A), 2-(3,4-dimethoxyphenyl)-2-isopropyl-5-[ (3,4-dimethoxyphanethyl)methylamino]valeronitrile, is used widely in the treatment of a variety of cardiovascular diseases, including paroxysmal superventricular tachycardia, angina and hypertension. 1-3 properties have attracted considerable interest .4-8 pharmaFologica1 effects have been enantiomers has been reported. 13-15 We sought heavy isotope labeled enantiomers Its pharmacologic, metabolic and pharmacokinetic Enantiomeric differences in and differential metabolism bf its