Equipotent allosteric effect of W84 on [3H]NMS-binding to cardiac muscarinic receptors from guinea-pig, rat, and pig.

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 3 mM MgHPO4, 50 mM Tris, pH 7.3, at 23 degrees. W84 inhibited [3H]NMS-binding in the three membrane suspensions with similar potency (half-inhibitory concentration IC50: 2-5 microM). To evaluate the allosteric activity of W84, its effect on the dissociation of [3H]NMS was determined. At 3 microM, W84 diminished the rate of [3H]NMS-dissociation to about 20% of the control in three suspensions. At 100 microM 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.