THE ANTIEPILEPTIC DRUG AWD-131-138 STIMULATES DIFFERENT RECOMBINANT ISOFORMS OF THE RAT GABA(A) RECEPTOR THROUGH THE BENZODIAZEPINE BINDING-SITE

Recombinant gamma-aminobutyric acid A (GABA(A)) receptors of the subun it compositions alpha 1 beta 2 gamma 2, alpha 1 beta 3 gamma 2, alpha 2 beta 2 gamma 2, alpha 3 beta 2 gamma 2 and (alpha 5 beta 2 gamma 2 w ere expressed in Xenopus oocytes in a functionally active form. At all subunit combinations, AWD 131-138 dose-dependently stimulated GABA cu rrents. At 10 mu M AWD 131-138, this allosteric stimulation amounted i n average to about 12-21% of the maximal stimulation achieved using di azepam. The threshold of stimulation was about 0.3-1.0 mu M. One micro meter of the benzodiazepine antagonist flumazenil (Ro 15-1788) counter acted the current stimulation by 10 mu M AWD 131-138, indicating that this drug acts at the binding site for benzodiazepines. (C) 1998 Elsev ier Science Ireland Ltd.