Equipotent Allosteric Effect of W84 on [3H]NMS‐Binding to Cardiac Muscarinic Receptors from Guinea‐Pig, Rat, and Pig*,**

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Abstract
W84 (hexamethylene‐bis‐[dimethyl‐(phthalimidopropyl)‐ammonium bromide]) is an experimental antidote against organophosphorus poisoning and has been found to affect muscarinic cholinoceptors allosterically. The attempt was made to test whether the W84‐action on muscarinic cholinoceptors depends on the species. For this purpose, the effect of W84 on the binding of [3H]N‐methylscopolamine ([3H]NMS) was investigated in membrane‐suspensions from the hearts of guinea pigs, rats, and pigs in 3mM MgHPO4, 50 mM Tris, pH 7.3, at 23°. W84 inhibited [3H]NMS‐binding in the three membrane suspensions with similar potency (half‐inhibitory concentration IC50: 2‐5μM). To evaluate the allosteric activity of W84, its effect on the dissociation of [3H]NMS was determined. At 3μM, W84 diminished the rate of [3H]NMS‐dissociation to about 20% of the control in the three suspensions. At 3μM of W84, [3H]NMS‐dissociation was almost prevented. In conclusion, W84 acted equally on the cardiac cholinoceptors of guinea pigs, rats, and pigs, respectively. It can be anticipated that M2‐cholinoceptors of other species would likewise be affected by W84.