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BAY u3405 an antagonist of thromboxane A 2 ‐ and prostaglandin D 2 ‐induced bronchoconstriction in the guinea‐pig
Author(s) -
Francis H.P.,
Greenham S.J.,
Patel U.P.,
Thompson A.M.,
Gardiner P.J.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12475.x
Subject(s) - bronchoconstriction , thromboxane a2 , leukotriene d4 , histamine , guinea pig , thromboxane , antagonist , chemistry , bay , prostaglandin d2 , prostaglandin , medicine , pharmacology , endocrinology , asthma , receptor , platelet , civil engineering , engineering
1 The novel thromboxane (TX) antagonist, BAY u3405, has been evaluated against bronchoconstriction induced by the TXA 2 mimetic U‐46619, prostaglandin D 2 (PGD 2 ), 5‐hydroxytryptamine (5‐HT), leukotriene D 4 (LTD 4 ) and histamine in the guinea‐pig in vivo by use of a modification of the model described by Konzett & Rössler. 2 When given intravenously (i.v.) at 30 or 100 μg kg −1 , U‐46619 caused 80% maximal bronchoconstriction in most animals. In contrast, PGD 2 caused a smaller 40%‐50% maximal bronchoconstriction at the highest dose tested (300 μg kg −1 , i.v.). 3 BAY u3405, given intravenously, orally (p.o.) or by aerosol antagonized U‐46619‐induced bronchoconstriction in a dose‐related manner. The approximate ID 50 values were 600 μg kg −1 , i.v., 1.7 mg kg −1 p.o. and 0.1% w/v 20 breaths by aerosol. 4 BAY u3405 had similar inhibitory activities against U‐46619‐induced bronchoconstriction and hypertension suggesting that it had no preferential activity on the airways. 5 When given intravenously BAY u3405 antagonized the bronchoconstrictor effect of intravenous PGD 2 with ID 50 values between 30–100 μg kg −1 . 6 The action of BAY u3405 (10 mg kg −1 , p.o.) was long lasting, causing significant inhibition of U‐46619‐induced bronchoconstriction 7 h after dosing. 7 At 1 mg kg −1 , i.v., a dose that abolished the response to U‐46619 and PGD 2 , BAY u3405 had no effect on histamine‐, 5‐HT‐ or LTD 4 ‐induced bronchoconstriction. 8 BAY u3405 potently and selectively antagonized U‐46619‐ or PGD 2 ‐induced bronchoconstriction in the Konzett‐Rössler model of guinea‐pig lung function. It should therefore prove to be a useful tool for defining the role of TXA 2 and PGD 2 in airway diseases such as asthma.