Modification by hexamethonium of the muscarinic receptors blocking activity of pancuronium and homatropine in isolated tissues of the guinea-pig

In the guinea-pig left atrium, hexamethonium (C6) (0.1-3 mM) caused a parallel rightward shift of concentration-response curves for the negative inotropic response to carbachol (CCh) and oxotremorine (Oxo), the dose ratios obtained with the latter agonist being significantly greater than those for CCh at all concentrations of C6 investigated. In the presence of C6, the muscarinic receptor blocking activity of homatropine (20 microM) or of pancuronium (0.3-2.7 microM) appears to be reduced but if the effect of hexamethonium on concentration-response curves to the agonists is taken into consideration, the dose ratios produced by the combination of C6 with either homatropine or pancuronium were essentially as predicted for the combination of 2 competitive antagonists. The difference in the affinity of pancuronium for cardiac muscarinic receptors and ileal muscarinic receptors was also reduced in the presence of hexamethonium (0.3 mM).