ACTIONS OF THIENYL ANALOGS OF BACLOFEN IN THE GUINEA-PIG ISOLATED ILEUM

In guinea-pig isolated ileal preparations, the 5-methylthien-2-yl (5d), 5-bromothien-2-yl (5f) and 5-chlorothien-2-yl (5h) analogs of baclofen depressed twitch responses to field stimulation in a dose-dependent manner. These actions were reversibly and competitively antagonised by 2-hydroxysaclofen but not by naloxone, phentolamine, propranolol or theophylline. The relative potencies (EC50 values) were baclofen (10-mu-M) > Sh (40-mu-M) > 5d (80-mu-M) > 5f (120-mu-M). These analogs represent a novel class of specific GABA(B) receptor agonists which, like baclofen, should readily enter the brain.