Octylonium bromide, an antagonist of platelet-activating factor.
Octylonium bromide, a spasmolytic agent in clinical use for the treatment of increased tone and/or motility of the gastrointestinal tract, was examined for its ability to antagonize some biological actions of platelet-activating factor. It was found capable of inhibiting, in a concentration- or dose-dependent fashion, the platelet-activating factor-induced platelet aggregation of rabbit platelet-rich plasma, bronchoconstriction in guinea-pigs, hypotension in rats and lethality in mice, its potency being between 1/15 and 1/50 that of WEB 2086. On the other hand, octylonium bromide was not capable of inhibiting the platelet-activating factor-induced contraction of guinea-pig lung parenchymal strips, an effect which is inhibited by WEB 2086 only at high concentrations. It is worth mentioning that octylonium bromide antagonized endotoxin-induced gastrointestinal damage, known to be due to platelet-activating factor release, at doses comparable to those which exert a spasmolytic effect in man. The role of platelet-activating factor in human gastrointestinal disorders has not yet been clearly established and, therefore, the clinical implications of this property of octylonium bromide are at the moment unknown.
Subissi
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Department of Pharmacology, Laboratori Guidotti S.p.A., Pisa, Italy.
Del Monte
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M
Evangelista
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Santicioli
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P
Criscuoli
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M
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects; D004731:Endotoxins; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000517:prevention & control; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology* / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D004731:Endotoxins; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D000644:Quaternary Ammonium Compounds; D014230:Triazoles; C052518:WEB 2086; C013934:octylonium; C037913:CV 3988