ALLOSTERIC MODULATION BY SINGLE ENANTIOMERS OF C3-CHIRAL 1,4-BENZODIAZEPINE OF THE GAMMA-AMINOBUTYRIC-ACID TYPE-A RECEPTOR-CHANNEL EXPRESSED IN XENOPUS OOCYTES

Xenopus laevis oocytes injected with Poly(A)(+)-RNA isolated from neur onal tissue express membrane proteins peculiar to tile origin of mRNA. The translation of gamma aminobutyric acid type A (GABA(A)) receptors has been shown by dose/ response behavior of GABA and the reversible blockade of the GABA-induced current by picrotoxin. This current was a nalyzed quantitatively under two electrode voltage-clamp conditions. T his methodology has been applied for the first time to study the funct ional properties of the receptor as a function of the stereochemistry of the ligands. The (+)-S and (-)-R enantiomers of a water-soluble ben zodiazepine derivative, 7-chloro-1,3-dihydro-3-hemisuccinyloxy-5-pheny l-1 ,4-benzodiazepin-2-one (OXHEM), obtained by preparative high perfo rmance liquid chromatographic (HPLC) resolution on chiral stationary p hase, act as agonists in the in vitro modulation of the chloride chann el. The (+)-S-OXHEM enantiomer was the more active. Chirality 9:286-29 0, 1997. (C) 1997 Wiley-Liss, Inc.