Article date: November 1991
By: H.P. Francis, S.J. Greenham, U.P. Patel, A.M. Thompson, P.J. Gardiner, in Volume 104, Issue 3, pages 596-602
The novel thromboxane (TX) antagonist, BAY u3405, has been evaluated against bronchoconstriction induced by the TXA2 mimetic U‐46619, prostaglandin D2 (PGD2), 5‐hydroxytryptamine (5‐HT), leukotriene D4 (LTD4) and histamine in the guinea‐pig in vivo by use of a modification of the model described by Konzett & Rössler.
When given intravenously (i.v.) at 30 or 100 μg kg−1, U‐46619 caused 80% maximal bronchoconstriction in most animals. In contrast, PGD2 caused a smaller 40%‐50% maximal bronchoconstriction at the highest dose tested (300 μg kg−1, i.v.).
BAY u3405, given intravenously, orally (p.o.) or by aerosol antagonized U‐46619‐induced bronchoconstriction in a dose‐related manner. The approximate ID50 values were 600 μg kg−1, i.v., 1.7 mg kg−1 p.o. and 0.1% w/v 20 breaths by aerosol.
BAY u3405 had similar inhibitory activities against U‐46619‐induced bronchoconstriction and hypertension suggesting that it had no preferential activity on the airways.
When given intravenously BAY u3405 antagonized the bronchoconstrictor effect of intravenous PGD2 with ID50 values between 30–100 μg kg−1.
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.
At 1 mg kg−1, i.v., a dose that abolished the response to U‐46619 and PGD2, BAY u3405 had no effect on histamine‐, 5‐HT‐ or LTD4‐induced bronchoconstriction.
BAY u3405 potently and selectively antagonized U‐46619‐ or PGD2‐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 TXA2 and PGD2 in airway diseases such as asthma.
The novel thromboxane (TX) antagonist, BAY u3405, has been evaluated against bronchoconstriction induced by the TXA2 mimetic U‐46619, prostaglandin D2 (PGD2), 5‐hydroxytryptamine (5‐HT), leukotriene D4 (LTD4) and histamine in the guinea‐pig in vivo by use of a modification of the model described by Konzett & Rössler.
When given intravenously (i.v.) at 30 or 100 μg kg−1, U‐46619 caused 80% maximal bronchoconstriction in most animals. In contrast, PGD2 caused a smaller 40%‐50% maximal bronchoconstriction at the highest dose tested (300 μg kg−1, i.v.).
BAY u3405, given intravenously, orally (p.o.) or by aerosol antagonized U‐46619‐induced bronchoconstriction in a dose‐related manner. The approximate ID50 values were 600 μg kg−1, i.v., 1.7 mg kg−1 p.o. and 0.1% w/v 20 breaths by aerosol.
BAY u3405 had similar inhibitory activities against U‐46619‐induced bronchoconstriction and hypertension suggesting that it had no preferential activity on the airways.
When given intravenously BAY u3405 antagonized the bronchoconstrictor effect of intravenous PGD2 with ID50 values between 30–100 μg kg−1.
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.
At 1 mg kg−1, i.v., a dose that abolished the response to U‐46619 and PGD2, BAY u3405 had no effect on histamine‐, 5‐HT‐ or LTD4‐induced bronchoconstriction.
BAY u3405 potently and selectively antagonized U‐46619‐ or PGD2‐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 TXA2 and PGD2 in airway diseases such as asthma.
DOI: 10.1111/j.1476-5381.1991.tb12475.x
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