STEREOSELECTIVE ACTIONS OF HALOTHANE AT GABA(A) RECEPTORS

Isoflurane anesthesia exhibits stereoselectivity, and a corresponding stereoselectivity ((+)->(-)-isomer) has been reported at GABA(A) recep tors in vitro. The objective of the present study was to determine if the positive modulatory actions of halothane at GABA(A) receptors exhi bited a similar stereoselectivity. Both (R)- and (S)-halothane ((+)- n d (-)- isomers, respectively) enhanced [H-3]flunitrazepam binding to b rain membranes in a concentration dependent manner without a significa nt difference in either potency (EC50) or efficacy (E-max). While both (R)- and (S)-halothane enhanced [H-3]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 < 0.0 2)). Thus, subtle structural differences between inhalational anesthet ics can have a significant impact on the degree of stereoselectivity a t the receptor level and may provide insights for the development of m ore specific drugs. (C) 1998 Published by Elsevier Science B.V.