Opposite effects of alcuronium on agonist and on antagonist binding to muscarinic receptors.
Alcuronium is known to retard allosterically the dissociation of [3H]N-methylscopolamine from muscarinic M2 receptors, thereby augmenting the binding of this antagonist. Functionally, alcuronium behaves as a weak antimuscarinic agent and induces in combination with N-methylscopolamine an overadditive antimuscarinic action with oxotremorine-M as the agonist. The effect of alcuronium on the binding of [3H]oxotremorine-M was studied in porcine heart homogenates. Agonist binding was concentration dependently inhibited with a Ki = 0.48 +/- 0.03 microM (means +/- S.D., n = 3). Under identical conditions [3H]N-methylscopolamine binding was elevated. Alcuronium, 100 microM, which nearly prevented the dissociation of [3H]N-methylscopolamine, retarded the rate of dissociation of [3H]oxotremorine-M only by a factor of two. These findings support the notion that the overadditive antimuscarinic action of alcuronium in conjunction with N-methylscopolamine is based on a shift by alcuronium of the interplay between agonist and antagonist in favour of the antagonist.
Maass
A
A
Department of Pharmacology and Toxicology, University of Bonn, Germany.
Mohr
K
K
D000443:Alcuronium / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D066298:In Vitro Techniques; D018721:Muscarinic Agonists / Q000378:metabolism*; D018727:Muscarinic Antagonists / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D019832:N-Methylscopolamine; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D010095:Oxotremorine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism; D013552:Swine
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D010095:Oxotremorine; D000443:Alcuronium; D019832:N-Methylscopolamine