Antagonism of baclofen-induced depression of whole-cell synaptic currents in spinal dorsal horn neurones by the potent GABA_B antagonist CGP55845

Abstract

The potencies of two GABA_B receptor antagonists P-[3-aminopropyl]-P-diethoxymethyl-phosphinic acid (CGP35348) and the novel compound 3-N[1-(S)-(3,4-dichlorophenyl)ethyl]amino-2-(S)-hydroxypropyl-P-benzyl-phosphinic acid (CGP55845) have been compared in an in vitro spinal cord preparation. They have been tested as antagonists of baclofen-induced depression of EPSCs of patch-clamped dorsal horn neurones following electrical stimulation of dorsal roots. Mean EC₅₀ values for the depressant action of baclofen were increased by 50- and 140-fold respectively in the presence of CGP35348 (200 μM) (n = 5) and CGP55845 (100 nM) (n = 4). This potency of CGP55845 is > 1000-fold higher than that reported previously for other GABA_B receptor antagonists.