Potentiation by alcuronium of the antimuscarinic effect of N-methylscopolamine in guinea pig left atria

Abstract

Alcuronium is known to stabilize allosterically the binding of the muscarinic antagonist N-methylscopolamine to muscarinic M 2 receptors and thus to elevate the equilibrium binding of N-methylscopolamine in homogenized cardiac tissue. In order to check for a functional consequence of this effect, the action of alcuronium alone and in combination with N-methylscopolamine was determined in contracting guinea pig left auricles with oxotremorine-M as the negative inotropic agonist. For sake of comparison, the allosteric modulator W84 = hexane-1,6-bis(dimethyl-3′-phthalimidopropyl-ammonium bromide) was included. Alcuronium displayed a weak antimuscarinic action (pA 2 = 5.7). In conjunction with 10 −7 M N-methylscopolamine, alcuronium (≥ 10 −6 M) induced a more pronounced antimuscarinic effect than expected for a combination of competitive antagonists. The extent of overadditivity with combinations of W84 and 10 −7 M N-methylscopolamine was smaller. In conclusion, alcuronium potentiates the antimuscarinic effect of N-methylscopolamine in contracting cardiac preparations with high effectivity.