Evaluation of rotenone and related compounds as antagonists of slow-reacting substance of anaphylaxis.
Rotenone (1), dihydrorotenone (2), isorotenone (3), mutarotenone (4), and deguelin (12) were found to be potent antagonists of slow-reacting substance of anaphylaxis (SRS-A) in vitro. However, these compounds were also shown to inhibit histamine, serotonin, and acetylcholine at only ten times their IC50 concentrations for SRS-A antagonism. Rotenone (1) and several related compounds were also evaluated in an in vivo guinea pig anaphylaxis model. Several of these compounds and FPL 55712 (I) were effective in prolonging collapse times of animals which received an aerosol challenge of an antigen to which they had been sensitized.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000707:Anaphylaxis / Q000503:physiopathology; D000818:Animals; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D012402:Rotenone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D013189:SRS-A / Q000037:antagonists & inhibitors*; D012702:Serotonin Antagonists
D006634:Histamine H1 Antagonists; D013189:SRS-A; D012702:Serotonin Antagonists; D012402:Rotenone; D000109:Acetylcholine