CGP 36216 is a selective antagonist at GABAB presynaptic receptors in rat brain

In rat neocortical preparations maintained in Mg2+-free Krebs medium, baclofen depressed the frequency of spontaneous discharges in a concentration-dependent 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 hyperpolarisations, mediated through gamma -aminobutyric acid, (GABA,) postsynaptic 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) postsynaptic receptors, it is appreciably more active at presynaptic receptors. (C) 2001 Elsevier Science B.V. All rights reserved.