Effect of DP-1904, a thromboxane synthetase inhibitor, on antigen- and spasmogen-induced bronchoconstriction in rodents

The effect of DP-1904 [6-(1-imidazolylmethyl)-5, 6, 7, 8-tetra-hydronaphtha lene-2-carboxylic acid hydrochloride], a selective thromboxane synthetase i nhibitor, was examined on antigen- and spasmogen-induced bronchoconstrictio n in rodents. Oral administration of DP-1901 (1, 3, 10 mg/kg) as well as OK Y-046 (sodium( E)-3[4-(1-imidazolylmethyl)-phenyl]-2-propanoate 100 mg/kg), significantly inhibited immunoglobulin G-mediated bronchoconstriction in a ctively sensitized guinea pigs. Immunoglobulin E-mediated bronchoconstricti on in actively sensitized rats was also inhibited by both DP-1904 (1, 10 mg /kg) and OKY-046 (100 mg/kg). DP-1904 (3-30 mg/kg) and OKY-046 (30 mg/kg) s uppressed leukotriene D-4-induced bronchoconstriction in guinea pigs. In th ese models, the endogenous levels of thromboxanes significantly increased f ollowing the stimulus (antigen and leukotriene D-4). DP-1904 (10 mg/kg) inh ibited the increase in thromboxane level in both plasma and bronchial alveo lar lavage fluid. These actions of DP-1904 persisted for more than 12 h, in dicating a long-lasting effect of DP-1904 on bronchoconstriction. The resul ts showed that the biological activity of DP-1904 in our rodents models is more potent than that of OKY-046 (Ozagrel), which is available as an anti-a sthma agent in Japan. (C) 1999 Elsevier Science B.V. All rights reserved.