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Abstract
Gallamine and d-tubocurarine inhibited (3H)N-methylscopolamine ((3H)NMS) binding to rat cardiac muscarinic receptors with I50 values of 0.7 μM and 22 μM, respectively. They decreased the association and dissociation rates of the two ligands (3H)NMS and (3H)Oxotremorine M ((3H)Oxo-M).
Gallamine interaction with muscarinic receptors was markedly inhibited by (3H)NMS and (3H)Oxo-M binding to the receptors. We were unable to demonstrate (3H)NMS or (3H)Oxo-M binding to the muscarinic receptor-gallamine complex.
By contrast, d-tubocurarine interaction with rat cardiac muscarinic receptors was facilitated by (3H)Oxo-M binding and only slightly inhibited by (3H)NMS binding to muscarinic binding sites. Furthermore, (3H)NMS and (3H)Oxo-M bound to the receptor-d-tubocurarine complex, indicating that the latter drug interacted with an allosteric site on cardiac muscarinic receptors but did not recognize the muscarinic binding site (at concentrations below 1 mM).