Evaluation of 3-aminopropanesulphonamide analogues of GABA as antagonists at GABA B receptors in peripheral and central preparations

Abstract

Cholinergic twitch responses in the guinea-pig isolated ileum, and spontaneous discharges in rat neocortical slices, were depressed by the GABA B receptor agonist baclofen. These actions were reversibly antagonised by the sulphonamide derivatives ( R, S)-2-hydroxy-3-phthalimidopropanesulphonamide (HPIPS), 3-amino- N-benzoylpropanesulphonamide (ABPS) and 3-phthalimidopropanesulphonamide (PIPS) which produced rightwards shifts of the baclofen concentration–response curves, with p A 2 values ranging between 4.1 and 4.3 in both preparations. From these results, HPIPS, ABPS and PIPS constitute a novel class of antagonists at GABA B hetero-receptors.