Stereoselective actions of halothane at GABA(A) receptors.

Isoflurane anesthesia exhibits stereoselectivity, and a corresponding stereoselectivity ((+)->(-)-isomer) has been reported at GABA(A) receptors in vitro. The objective of the present study was to determine if the positive modulatory actions of halothane at GABA(A) receptors exhibited a similar stereoselectivity. Both (R)- and (S)-halothane ((+)- and (-)- isomers, respectively) enhanced [3H]flunitrazepam binding to brain membranes in a concentration dependent manner without a significant difference in either potency (EC50) or efficacy (Emax). While both (R)- and (S)-halothane enhanced [3H]muscimol binding, the potency of the (+)-isomer was slightly greater than the corresponding (-)-isomer (0.91 +/- 0.17 versus 1.45 +/- 0.04% atmospheres, respectively (P < 0.02)). Thus, subtle structural differences between inhalational anesthetics can have a significant impact on the degree of stereoselectivity at the receptor level and may provide insights for the development of more specific drugs.