Inhibition of experimental immediate hypersensitivity reactions by a novel xanthone, RU 31156.
RU 31156, the tris-(hydroxymethyl)-aminomethane salt of 7-(S-methylsulphonimidoyl)-5-(n-hexyl)-xanthen-9-one-2-carboxylic acid has been found to be a potent inhibitor of experimental immediate hypersensitivity reactions in vivo. In the IgE-mediated rat PCA test, RU 31156 had an ED50 of 0.0046 (00037--0.0057) mg/kg which compared to a figure of 1.21 (1.04--1.42) mg/kg for disocium cromoglycate (DSCG), both compounds being administered intravenously. RU 31156 was also active when administered orally, having an ED50 of 0.19 (0.07--0.30) mg/kg when given 10 min before antigen. RU 31156 partially inhibited an IgG-mediated PCA reaction in the rat. Both RU 31156 and DSCG inhibited anaphylactic bronchoconstriction in the rat, giving bell-shaped dose-response curves. From the upward part of the curves, approximate ED30 values of 0.02 and 2.0 mg/kg were obtained for RU 31156 AND DSCG respectively. Anaphylactic bronchoconstriction in the guinea-pig was not affected by RU 31156 and pinnal anaphylaxis was inhibited at only relatively high doses of 1--10 mg/kg i.v. The effects of both histamine and 5-hydroxytryptamine in the mouse pinna were not affected by RU 31156. In PCA experiments, RU 31156 showed self-tachyphylaxis following both intravenous and oral administration. It also showed cross-tachyphylaxis with DSCG, indicating that these compounds are likely to share a similar mode of action.
D000707:Anaphylaxis / Q000188:drug therapy; D000818:Animals; D001986:Bronchial Spasm / Q000188:drug therapy; D004423:Ear / Q000187:drug effects; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists; D006969:Hypersensitivity, Immediate / Q000188:drug therapy*; D008297:Male; D051379:Mice; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D051381:Rats; D012702:Serotonin Antagonists; D013618:Tachyphylaxis; D013997:Time Factors; D014325:Tromethamine / Q000494:pharmacology; D014966:Xanthenes / Q000494:pharmacology / Q000627:therapeutic use*
D006634:Histamine H1 Antagonists; D012702:Serotonin Antagonists; D014966:Xanthenes; D014325:Tromethamine; C016874:RU 31156