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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Novel arylaminopyridazine-GABA receptor antagonists examined electrophysiologically in Ascaris suum.

The structure-activity relationships of 35 novel derivatives of 2-(carboxypropyl)-3-amino-4-methyl-6-phenyl pyridazine (SR 95103) were examined as gamma-aminobutyric acid (GABA) antagonists in the flap preparation of the parasitic nematode, Ascaris suum, using a two-microelectrode current-clamp technique. All but one of the potent antagonists displaced GABA dose-response curves to the right without reduction in the maximum response. The dissociation constants of the more potent competitive antagonists were described using a model which assumed that two molecules of GABA were required to open the ion channel but that only one molecule of antagonist acted on each ion channel. By exploring the structure-activity relationship, the potency of the antagonist was increased from a KB of 64 microM for SR 95103 to a KB of 4.7 microM for NCS 281-93 (2-(3-carboxypropyl)-3-amino-4-phenylpropyl-6-phenyl pyridazine).[1]


  1. Novel arylaminopyridazine-GABA receptor antagonists examined electrophysiologically in Ascaris suum. Martin, R.J., Sitamze, J.M., Duittoz, A.H., Wermuth, C.G. Eur. J. Pharmacol. (1995) [Pubmed]
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