Antagonism at GABA B receptors by saclofen and related sulphonic analogues of baclofen and GABA

Abstract

Saclofen (the direct sulphonic analogue of baclofen) is a competitive antagonist of baclofen at GABA B receptors in guinea pig ileum and rat cortical slices (estimated pA 2 = 5.3), at least twice as potent as 2-hydroxy-saclofen (pA 2 = 5). A series of related sulphonic analogues also antagonised baclofen in the guinea pig ileum, including 2-hydroxy-saclofen amide (pA 2 = 3.3), 3-amino-2-hydroxy-2-phenyl-propylsulphonic acid (pA 2 = 3.5), 3-amino-2-(benzo-(b)-furan-2-yl)-propylsulphonic acid (pA 2 = 4.3), and 3-amino-2-(4-chlorophenyl)-prop-l-enesulphonic acid (pA 2 = 2.5–3), but none were more active than saclofen which is the most potent specific GABA B antagonist yet found.