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.
Mohr
K
K
Department of Pharmacology, University of Kiel, Germany.
Staschen
C M
CM
Ziegenhagen
M
M
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D054833:Isoindoles; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D019832:N-Methylscopolamine; D010276:Parasympatholytics / Q000378:metabolism*; D010797:Phthalimides / Q000494:pharmacology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012602:Scopolamine Derivatives / Q000378:metabolism*; D013045:Species Specificity; D013552:Swine
D002800:Cholinesterase Inhibitors; D054833:Isoindoles; D010276:Parasympatholytics; D010797:Phthalimides; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; C013017:hexamethylenebis(dimethyl-(3-phthalimidopropyl)ammonium bromide); D019832:N-Methylscopolamine