THE (S)-ENANTIOMER OF 2-HYDROXYSACLOFEN IS THE ACTIVE GABA(B) RECEPTOR ANTAGONIST IN CENTRAL AND PERIPHERAL PREPARATIONS

In the guinea-pig isolated ileum, (RS)-(+/-)-baclofen induced a depres sion of cholinergic twitch contractions, reversibly and competitively antagonised by (S)-2-hydroxysaclofen (pA(2) = 5.2 +/- 0.2), but not by (R)-2-hydroxysaclofen. The depression of excitatory field potentials by baclofen (5 mu M) in rat CA1 hippocampal slices was antagonised by (S)-2-hydroxysaclofen (100 mu M) (pA(2) = 4.3), whilst in rat neocorte x, (S)-2-hydroxysaclofen (50-500 mu M) antagonised the baclofen (10 mu M)-induced suppression of spontaneous discharges, the (R)-enantiomer being inactive. These results show that (S)-2-hydroxysaclofen is the a ctive antagonist at central and peripheral GABA(A) receptors.