Correlation of brain levels of barbiturate enantiomers with reported differences in duration of sleep

The concentrations of R(+)-and S(-)-pentobarbital and R(+)-and S(-)-secobarbital were determined in the brain stem, hypothalamus, cerebellum and cortex of mice after i.v. administration. No regional differences in enantiomer concentration or barbiturate/metabolite ratio were observed to account for the substantial potency differences reported for the enantiomeric forms of pentobarbital and secobarbital. Stereoselective differences in the rate of enantiomer metabolism and in stereochemical fit to the central nervous system receptor are discussed as possible reasons for the differences in duration of action.