Antagonism at GABAB receptors by saclofen and related sulphonic analogues of baclofen and GABA.
Saclofen (the direct sulphonic analogue of baclofen) is a competitive antagonist of baclofen at GABAB receptors in guinea pig ileum and rat cortical slices (estimated pA2 = 5.3), at least twice as potent as 2-hydroxy-saclofen (pA2 = 5). A series of related sulphonic analogues also antagonised baclofen in the guinea pig ileum, including 2-hydroxy-saclofen amide (pA2 = 3.3), 3-amino-2-hydroxy-2-phenyl-propylsulphonic acid (pA2 = 3.5), 3-amino-2-(benzo-(b)-furan-2-yl)-propylsulphonic acid (pA2 = 4.3), and 3-amino-2-(4-chlorophenyl)-prop-1-enesulphonic acid (pA2 = 2.5-3), but none were more active than saclofen which is the most potent specific GABAB antagonist yet found.
Kerr
D I
DI
Department of Anaesthesia and Intensive Care, University of Adelaide, Australia.
Ong
J
J
Johnston
G A
GA
Abbenante
J
J
Prager
R H
RH
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D058787:GABA-A Receptor Antagonists; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation*; D011963:Receptors, GABA-A / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; C057491:2-hydroxysaclofen