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

Abstract

In rat neocortical preparations maintained in Mg 2+-free Krebs medium, baclofen depressed the frequency of spontaneous discharges in a concentration-dependent manner (EC 50=6 μM), sensitive to (3-aminopropyl)ethylphosphinic acid (CGP 36216) (100, 300 and 500 μM) (p A 2=3.9±0.1). By contrast, CGP 36216, up to 1 mM, was ineffective in antagonising baclofen-induced hyperpolarisations, mediated through γ-aminobutyric acid B (GABA B) postsynaptic receptors. In electrically stimulated brain slices preloaded with [ 3H]GABA, CGP 36216 increased [ 3H]GABA release (IC 50=43 μM), which was reversed by baclofen (20 μM). While CGP 36216 is ineffective at GABA B postsynaptic receptors, it is appreciably more active at presynaptic receptors.