BAY u3405 an antagonist of thromboxane A2- and prostaglandin D2-induced bronchoconstriction in the guinea-pig.

1. 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. 2. When given intravenously (i.v.) at 30 or 100 micrograms 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 micrograms 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 ID50 values were 600 micrograms 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 PGD2 with ID50 values between 30-100 micrograms 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 PGD2, BAY u3405 had no effect on histamine-, 5-HT- or LTD4-induced bronchoconstriction. 8. 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.

Comparative effects of carprofen, benoxaprofen and indomethacin on the development and decay phases of a carrageenan pleurisy in the rat.

The effects of three non-steroidal anti-inflammatory drugs (NSAID), carprofen, benoxaprofen and indomethacin, on 4-hour and 24-hour carrageenan pleurisy, has been investigated. All three compounds inhibited both the oedematous and cellular components of the 4-hour pleurisy. In the 24-hour pleurisy only indomethacin affected cell accumulation and the inhibitory effect observed was selective for mononuclear cells. The volume of exudate recovered from the pleural cavity at 24 hours, in animals which had received any of the three drugs, was greater than in animals receiving vehicle. The results of a time-course experiment with indomethacin suggest that the observed effects of the NSAID may be a consequence of their inhibition of both the development and decay phases of the pleural inflammation, particularly with regard to the exudative component of the response.