The antiepileptic drug AWD 131-138 stimulates different recombinant isoforms of the rat GABA(A) receptor through the benzodiazepine binding site

  • Neurosci Lett. 1998 Apr 3;245(2):85-8. doi: 10.1016/s0304-3940(98)00186-4.
E Sigel  1 ,  R Baur ,  R Netzer ,  C Rundfeldt
Affiliations
PMID: 9605491 DOI: 10.1016/s0304-3940(98)00186-4
Abstract

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.

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