ANTAGONISM OF BACLOFEN-INDUCED DEPRESSION OF WHOLE-CELL SYNAPTIC CURRENTS IN SPINAL DORSAL HORN NEURONS BY THE POTENT GABA(B) ANTAGONIST CGP55845

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 mu M) (n=5) and CGP55845 (100 nM) (n=4). This potency of CGP55845 is >1000-fold higher than that reported previously for other GABA, receptor antagonists.