Octylonium bromide: a smooth muscle relaxant which interferes with calcium ions mobilization.
A series of "in vitro" experiments have been carried out to determine the mechanisms(s) responsible for the smooth muscle relaxant properties exhibited by octylonium bromide. Unlike N-butyl-scopolammonium bromide, octylonium bromide possesses both competitive and non competitive antimuscarinic and antihistaminic properties. Pretreatment of ileal segments with dibenamie, which destroyed muscarinic spare receptors, revealed the non competitive nature of octylonium bromide antagonism. The competitive antagonism toward BaCl2-induced contraction of rat ileum and aorta suggested that octylonium bromide interferes with Ca++ mobilization. As compared with verapamil a known Ca++ entry blocker and unlike it, octylonium bromide is more effective in antagonizing Ca++-induced contraction in K+ depolarized rat colon than aorta. Both octylonium bromide and verapamil reduced in a concentration-dependent manner the tonic contraction produced by exposure to high K+ of rat duodenum and rabbit ear artery. Both octylonium bromide and verapamil antagonized carbachol-induced phasic plus sustained tonic contraction of rat colon in high K+ Ca++-free medium. Unlike octylonium bromide, verapamil antagonized the phasic contraction only and inhibition of the overall contraction did not exceed 60%. Unlike verapamil, octylonium bromide antagonized norepinephrine-induced contraction of rabbit ear artery in high K+ C++-free medium. Interference with mobilization of cellular and extracellular Ca++ pools produced by different neurohormones is likely to be the mechanism responsible for octylonium bromide smooth muscle relaxant properties in both animals and humans.
D000818:Animals; D002121:Calcium Channel Blockers; D002122:Calcium Chloride / Q000494:pharmacology; D003983:Dibenzylchlorethamine / Q000494:pharmacology; D004347:Drug Interactions; D004386:Duodenum / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010276:Parasympatholytics; D000644:Quaternary Ammonium Compounds; C013934:octylonium; D003983:Dibenzylchlorethamine; D006632:Histamine; C028530:furtrethonium; D014700:Verapamil; D002122:Calcium Chloride