Thioether analogues of baclofen, phaclofen and saclofen

Abstract Analogues of baclofen, phaclofen and saclofen, incorporating a sulfur atom within the methylene chain, have been tested against responses induced by baclofen for activity at γ-aminobutyric acid-B (GABA B ) receptor sites, using a number of preparations including the guinea-pig isolated ileum and vas deferens, rat brain cortical slices and displacement of (−)-[ 3 H]baclofen in rat cerebellar membranes. Results indicate that 2-{[2-amino-1-(4-chlorophenyl)ethyl]thio}ethanephosphonic acid 2d is the most active of the new compounds. 2d is some 2–5 times weaker than phaclofen as a GABA B antagonist and approximately half as potent as phaclofen as an inhibitor of GABA B binding.