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

Cholinergic twitch responses in the guinea-pig isolated ileum, and spontane ous discharges in rat neocortical slices, were depressed by the GABA(B) rec eptor agonist baclofen. These actions were reversibly antagonised by the su lphonamide derivatives (R,S)-2-hydroxy-3-phthalimidopropanesulphonamide (HP IPS), 3-amino-N-benzoylpropanesulphonamide (ABPS) and 3-phthalimidopropanes ulphonamide (PIPS) which produced rightwards shifts of the baclofen concent ration-response curves, with pA(2) values ranging between 4.1 and 4.3 in bo th preparations. From these results, HPIPS, ABPS and PIPS constitute a nove l class of antagonists at GABA, hetero-receptors. (C) 1999 Elsevier Science B.V. All rights reserved.