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 M2 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 (pA2 = 5.7). In conjunction with 10(-7) M N-methylscopolamine, alcuronium (> or = 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.
Maass
A
A
Department of Pharmacology and Toxicology, University of Bonn, Germany.
Kostenis
E
E
Mohr
K
K
D000443:Alcuronium / Q000494:pharmacology*; D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D016275:Atrial Function; D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003198:Computer Simulation; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D054833:Isoindoles; D009200:Myocardial Contraction / Q000187:drug effects; D019832:N-Methylscopolamine; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology; D010276:Parasympatholytics / Q000378:metabolism / Q000494:pharmacology*; D010797:Phthalimides / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012044:Regression Analysis; D012602:Scopolamine Derivatives / Q000378:metabolism / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D054833:Isoindoles; D010276:Parasympatholytics; D010797:Phthalimides; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; C013017:hexamethylenebis(dimethyl-(3-phthalimidopropyl)ammonium bromide); D010095:Oxotremorine; C042743:oxotremorine M; D000443:Alcuronium; D019832:N-Methylscopolamine