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

Rat recombinant alpha 1 beta 2 gamma 2 gamma-aminobutyric acid type A (GABA A) receptors were functionally expressed in Xenopus laevis oocytes and anal yzed for the action of EDPC (Ethyl 3-(1,3-dithian-2-yl)-1H-pyrrolo[2,3-c] p yridine-5-carboxylate) using electrophysiological techniques. EDPC inhibite d GABA currents at low concentrations (IC50 approximate to 2 nM). The inhib ition by 100 nM EDPC could be reversed by 1 mu M of the benzodiazepine anta gonist flumazenil (Ro 15-1788), indicating a negative allosteric modulation via the benzodiazepine binding site. In line with this conclusion are radi oactive ligand binding studies. EDPC inhibited the binding of 2 nM [H-3]flu nitrazepam to membranes from the cerebellum or the cortex with IC50 values of about 8 and 25 nM, respectively. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.