Modulation of a GABA-ergic inhibitory circuit in the in vitro hippocampus by etomidate isomers.

A pulse-paired stimulation technique was used to examine the in vitro effects of the isomers of etomidate on synaptic transmission between Schaffer collaterals and CA1 pyramidal cells in the guinea pig hippocampus. Etomidate produced a dose-related, stereospecific, reversible increase in paired-pulse inhibition. Replacement of Cl- by isethionate reversed the inhibition induced by (+)-etomidate. Together with earlier biochemical evidence, these results show that in the mammalian CNS (+)-etomidate enhances central inhibition by increasing the effectiveness of gamma-aminobutyric acid (GABA) in a chloride-dependent fashion.