Opposite effects of alcuronium on agonist and on antagonist binding to muscarinic receptors

Eur J Pharmacol. 1996 Jun 3;305(1-3):231-4. doi: 10.1016/0014-2999(96)00240-3.

Abstract

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.

MeSH terms

  • Alcuronium / pharmacology*
  • Animals
  • Cell Membrane / metabolism
  • In Vitro Techniques
  • Muscarinic Agonists / metabolism*
  • Muscarinic Antagonists / metabolism*
  • Myocardium / metabolism
  • N-Methylscopolamine
  • Nicotinic Antagonists / pharmacology*
  • Oxotremorine / metabolism
  • Protein Binding / drug effects
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / metabolism*
  • Scopolamine Derivatives / metabolism
  • Swine

Substances

  • Muscarinic Agonists
  • Muscarinic Antagonists
  • Nicotinic Antagonists
  • Receptors, Muscarinic
  • Scopolamine Derivatives
  • Oxotremorine
  • Alcuronium
  • N-Methylscopolamine