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 subunit compositions alpha1beta2gamma2, alpha1beta3gamma2, alpha2beta2gamma2, alpha3beta2gamma2 and alpha5beta2gamma2 were expressed in Xenopus oocytes in a functionally active form. At all subunit combinations, AWD 131-138 dose-dependently stimulated GABA currents. At 10 microM AWD 131-138, this allosteric stimulation amounted in average to about 12-21% of the maximal stimulation achieved using diazepam. The threshold of stimulation was about 0.3-1.0 microM. One micrometer of the benzodiazepine antagonist flumazenil (Ro 15-1788) counteracted the current stimulation by 10 microM AWD 131-138, indicating that this drug acts at the binding site for benzodiazepines.
Sigel
E
E
Department of Pharmacology, University of Bern, Switzerland. sigel@pki.unibe.ch
Baur
R
R
Netzer
R
R
Rundfeldt
C
C
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001569:Benzodiazepines / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects; D058785:GABA-A Receptor Agonists; D007093:Imidazoles / Q000494:pharmacology*; D009865:Oocytes; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism*; D014981:Xenopus
C116306:AWD 131-138; D000927:Anticonvulsants; D058785:GABA-A Receptor Agonists; D007093:Imidazoles; D020033:Protein Isoforms; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D001569:Benzodiazepines