Short-chain baclofen analogues are GABAB receptor antagonists in the guinea-pig isolated ileum.
A new series of GABAB receptor antagonists, based on short-chain baclofen analogues has been investigated. In guinea-pig isolated ileal preparations, the GABAB receptor-mediated, baclofen-induced depression of cholinergic twitch responses was reversibly and competitively antagonised by the short-chain baclofen analogues 3-amino-3-(p-chlorophenyl)propionic acid (apparent pA2 = 3.5), 2-amino-2-(p-chlorophenyl)ethanephosphonic acid (apparent pA2 = 3.8), and 2-amino-2-(p-chlorophenyl)ethanesulphonic acid apparent pA2 = 4.0). The corresponding des-chloro analogues were all less active. These compounds represent another class of GABAB receptor antagonists which may cross the blood-brain barrier.
Ong
J
J
Department of Anaesthesia and Intensive Care, University of Adelaide, Australia.
Kerr
D I
DI
Abbenante
J
J
Prager
R H
RH
D000615:Aminoethylphosphonic Acid / Q000031:analogs & derivatives; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D058787:GABA-A Receptor Antagonists; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D013654:Taurine / Q000031:analogs & derivatives; D015091:beta-Alanine / Q000031:analogs & derivatives
D058787:GABA-A Receptor Antagonists; C075070:2-amino-2-(4-chlorophenyl)ethanesulfonic acid; D015091:beta-Alanine; C064718:3-amino-3-phenylpropionic acid; D013654:Taurine; D010649:Phenylalanine; D000615:Aminoethylphosphonic Acid; D001418:Baclofen