EDPC: a novel high affinity ligand for the benzodiazepine site on rat GABA(A) receptors

Rat recombinant alpha1beta2gamma2 gamma-aminobutyric acid type A (GABAA) receptors were functionally expressed in Xenopus laevis oocytes and analyzed for the action of EDPC (Ethyl 3-(1,3-dithian-2-yl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate) using electrophysiological techniques. EDPC inhibited GABA currents at low concentrations (IC50 approximately/= 2 nM). The inhibition by 100 nM EDPC could be reversed by 1 microM of the benzodiazepine antagonistflumazenil (Ro 15-1788), indicating a negative allosteric modulation via the benzodiazepine binding site. In line with this conclusion are radioactive ligand binding studies. EDPC inhibited the binding of 2 nM [3H]flunitrazepam to membranes from the cerebellum or the cortex with IC50 values of about 8 and 25 nM, respectively.