CGP 36216 is a selective antagonist at GABA(B) presynaptic receptors in rat brain

In rat neocortical preparations maintained in Mg2+-free Krebs medium, baclo fen depressed the frequency of spontaneous discharges in a concentration-de pendent manner (EC50 = 6 muM), sensitive to (3-aminopropyl)ethylphosphinic acid (CGP 36216) (100, 300 and 500 muM) (pA(2) = 3.9 +/- 0.1). By contrast, CGP 36216, up to I mM, was ineffective in antagonising baclofen-induced hy perpolarisations, mediated through gamma -aminobutyric acid, (GABA,) postsy naptic receptors. In electrically stimulated brain slices preloaded with [H -3]GABA(A) CGP 36216 increased [H-3]GABA release (IC50 = 43 muM), which was reversed by baclofen (20 muM). While CGP 36216 is ineffective at GABA(B) p ostsynaptic receptors, it is appreciably more active at presynaptic recepto rs. (C) 2001 Elsevier Science B.V. All rights reserved.