3-AMINO-2-(4-CHLOROPHENYL)-NITROPROPANE IS A NEW GABA(B) RECEPTOR AGONIST, MORE ACTIVE PERIPHERALLY

The activity of the nitropropane analog of baclofen, 3-amino-2-(4-chlorophenyl)-nitropropane (N-BAC), has been examined at central and peripheral GABA(B) receptors. N-BAC was less potent than baclofen as a GABA(B) receptor agonist in depressing repetitive twitch contractions in the guinea-pig isolated ileum (IC50s for baclofen = 4.1 +/- 1.3 muM; N-BAC = 9.2 +/- 0.3 muM) and vas deferens (IC50s for baclofen = 30 muM; N-BAC = 100 muM), competitively antagonised by phaclofen, 2-hydroxysaclofen and CGP 35348 (3-aminopropyl-P-di-ethoxymethylphosphinic acid). In the ileum, the pA2 values for CGP 35348 with baclofen (4.7 +/- 0.2) and N-BAC (4.6 +/- 0.3) were not significantly different (P > 0.05), indicating that both agonists activate the same receptor type. By contrast, in rat neocortical slices, N-BAC was 20 times weaker than baclofen in attenuating spontaneous discharges, sensitive to CGP 35348, whilst it was 100 times less potent than baclofen in depressing evoked CA1 population spikes in the hippocampus. This new GABA(B) receptor agonist, N-BAC, is thus more active at peripheral than central GABA(B) receptors.