POTENTIATION BY ALCURONIUM OF THE ANTIMUSCARINIC EFFECT OF N-METHYLSCOPOLAMINE IN GUINEA-PIG LEFT ATRIA

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'-phtharimidopropyl-ammonium bromide) was included. Alcuronium displayed a weak antimuscarinic action (pA(2) = 5.7). In conjunction with 10(-7) M N-methylscopolamine, alcuronium (greater than or equal to 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.