GBBA(B) receptor antagonism by 7-MBFG, a benzo[b]furan analogue of baclofen, in central and peripheral tissues

(R,S)-4-Amino-3-(7-methylbenzo[b]furan-2-yl)-butanoic acid (7-MBFG), a new benzofuran analogue of the GABA(B) receptor agonist baclofen, has been eval uated for pharmacological activity on GABA(B) receptors in the guineapig is olated ileum and rat neocortical slices. 7-MBFG (300 and 500 mu M) reversib ly antagonized the (R,S)-baclofen induced depression of cholinergic twitch contractions in the guinea-pig ileum and shifted the concentration-response curve for baclofen to the right, in a parallel manner, giving an apparent pA(2) value of 3.7 +/- 0.3. Likewise, 7-MBFG (300 and 500 mu M) reversibly blocked the baclofen-induced suppression of spontaneous discharges, in rat neocortical slices maintained in Mg2+-free Krebs medium, and caused a right ward, parallel shift of the baclofen concentration-response curve, giving a n apparent pA(2) value of 4.1 +/- 0.1. The compound 7-MBFG belongs to a nov el, new class of antagonist at central and peripheral GABAB receptors, in w hich the antagonist properties reside in the pseudo-aromatic character of t heir 3-benzo[b]furan-2-yl substituents, and might provide useful leads for further development of GABA(B) receptor ligands.