Abstract

Stereoselectivity in the microsomal metabolism of hexobarbital has been investigated. In both male and female rats l-hexobarbital has a longer latency, has a longer half-life and achieves higher blood levels after equivalent doses of the two enantiomers. The l-enantiomer is a more potent anesthetic in females but produces approximately equal sleeping times in male rats. The reason for the similar biologic potency in males despite a faster rate of metabolism of the d-enantiomer is not clear. Studies of microsomal metabolism indicate that male rats metabolize d-hexobarbital faster than the l-enantiomer and that males metabolize both optically active forms faster than females. Pretreatment with phenobarbital, but not 3-methylcholanthrene, always resulted in increased rates of metabolism for both enantiomers. Experiments with SKF 525A as an inhibitor of microsomal metabolism point out the need to consider the role of stereochemistry in inhibition studies.