title: Stereoselective actions of halothane at GABA(A) receptors.
abstract: 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.
authors.affiliation: Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892-0008, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Harris
authors.forename: E J
authors.initials: EJ
authors.lastname: Moody
authors.forename: P
authors.initials: P
authors.lastname: Skolnick
mesh_terms: D018685:Anesthetics, Inhalation / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D004347:Drug Interactions; D005445:Flunitrazepam / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D006221:Halothane / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D018685:Anesthetics, Inhalation; D018755:GABA Agonists; D018757:GABA Modulators; D011963:Receptors, GABA-A; D009118:Muscimol; D005445:Flunitrazepam; D006221:Halothane