3-amino-2-(4-chlorophenyl)-nitropropane is a new GABAB 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 GABAB receptors. N-BAC was less potent than baclofen as a GABAB receptor agonist in depressing repetitive twitch contractions in the guinea-pig isolated ileum (IC50s for baclofen = 4.1 +/- 1.3 microM; N-BAC = 9.2 +/- 0.3 microM) and vas deferens (IC50s for baclofen = 30 microM; N-BAC = 100 microM), 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 GABAB receptor agonist, N-BAC, is thus more active at peripheral than central GABAB receptors.
Department of Anaesthesia and Intensive Care, University of Adelaide, South Australia.
D I
DI
Kerr
J
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Ong
D J
DJ
Doolette
J
J
Abbenante
R H
RH
Prager
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects*; D058787:GABA-A Receptor Antagonists; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009574:Nitro Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011437:Propylamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects
D058787:GABA-A Receptor Antagonists; D009574:Nitro Compounds; D009943:Organophosphorus Compounds; D011437:Propylamines; D011963:Receptors, GABA-A; C081953:3-amino-2-(4-chlorophenyl)nitropropane; C066430:CGP 35348; D001418:Baclofen