Stereoselective anticonvulsant activity of the enantiomers of (±)-2-hydroxy-2-phenylbutyramide

The enantiomers of the anticonvulsant DL-2-hydroxy-2-phenylbutyramide (1) were prepared by resolving the (-)-quinine and (+)-1-phenylethylamine salts of the acids. The optically active acids were then esterified and reacted with ammonia to give (+)-1 and (-)-1. Optical purity of the amides was greater than 99.9% enantiomeric excess by chiral HPLC. Examination of the infrared spectra of the enantiomers and the racemate of 1 in chloroform solution showed identical spectra, but the spectrum of the racemate in a KBr disc was somewhat different from those of the pure enantiomers. Pharmacologically, 1 and its enantiomers have a similar significant anticonvulsant activity at peak drug effect against pentylenetetrazol seizures, but a variation in the time between the enantiomers was found with the anticonvulsant activity. In the rotarod ataxia test (-)-1-possessed the lowest neurotoxicity.