WY-50, 295 tromethamine: an orally active 5-lipoxygenase inhibitor with anti-allergic activity.
WY-50,295 tromethamine inhibited antigen-induced peptidoleukotriene (pLT) release from fragmented sensitized guinea pig lung (IC50 = 0.63 microM), antagonized LTD4-induced contractions of isolated guinea pig trachea (pA2 = 6.06), and suppressed antigen-induced contraction of sensitized guinea pig trachea over the 0.1-10 microM concentration range. In vivo, WY-50,295 tromethamine inhibited LTD4-induced bronchoconstriction (ED50 = 1.3 mg/kg i.v. and 6.6 mg/kg p.o.) and antigen-induced bronchoconstriction (ED50 = 2.5 mg/kg i.v. and 7.3 mg/kg p.o.) in anesthetized guinea pigs. Peak activity vs antigen was noted at 4-6 h after oral dosing and remained significant through 18 h. These studies demonstrate that WY-50,295 tromethamine possesses the complimentary actions of 5-LO inhibition and LTD4 receptor antagonism.
Weichman
B M
BM
Wyeth-Ayerst Research, Princeton, New Jersey 08543-8000.
Berkenkopf
J W
JW
Chang
J Y
JY
Heaslip
R J
RJ
Kreft
A F
AF
Lewis
A J
AJ
Musser
J H
JH
Grimes
D
D
D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000503:physiopathology*; D015289:Leukotrienes / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009280:Naphthaleneacetic Acids / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D013189:SRS-A / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D000941:Antigens; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D009280:Naphthaleneacetic Acids; D011804:Quinolines; D013189:SRS-A; C067525:S(alpha)-methyl-6-(2-quinolinylmethoxy)-2-naphthaleneacetic acid