Antagonism of baclofen-induced depression of whole-cell synaptic currents in spinal dorsal horn neurones by the potent GABAB 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 EC 50 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.