BRONCHOPULMONARY ACTIONS OF -(1,2,3,4-TETRAHYDRO-1-NAPHTHYLENYL)-1H-IMIDAZOLE, NITRIC-ACID SALT (LY150310), A SUBSTITUTED IMIDAZOLE, IN THEGUINEA-PIG

-(1,2,3,4-tetrahydro-1-naphthylenyl)-1H-imidazole, nitric acid salt (L Y150310), was examined for bronchodilator activity in the guinea pig. In guinea pig tracheal preparations, LY1 5031 0 competitively antagoni zed the contractile effects of exogenous histamine and blocked the his tamine-mediated component of contractions produced by ovalbumin challe nge. LY1 5031 0 had little effect on the nonhistamine component of ova lbumin-induced contractions of lung parenchymal strips, but it enhance d the production of prostaglandin (PG) E2 and PGF2alpha although it pa rtially inhibited thromboxane B2 formation. In other studies, in which postmortem pulmonary gas trapping was used as an index of in vivo air way obstruction, i.v. LY150310 dose-dependently inhibited the bronchos pasm produced by aerosols of the divalent cationic ionophore A23187, h istamine, 5-hydroxytryptamine, leukotriene D4, methacholine, ovalbumin or platelet activating factor. LY1 5031 0 was equal to or more potent than aminophylline in all test systems. Also, orally administered LY1 50310 inhibited the airway obstruction produced by selected challenge aerosols. In ex vivo studies, LY150310 elevated PGE2 and tended to dec rease thromboxane B2 in sodium arachidonate-stimulated whole blood. Ho wever, PGE2 and other cyclooxygenase products did not appear to accoun t for in vivo bronchodilation, because combining LY 1 5031 0 and pirox icam did not alter inhibition of A23187-induced airway obstruction. Ou r results demonstrate that LY150310 reduces airway obstruction caused by a variety of bronchoconstrictive agents, including A23187 and ovalb umin. Although this substituted imidazole appears to have activity as a histamine H-1-receptor antagonist and can alter prostanoid concentra tions in vitro and in vivo, its mode of bronchodilation is unclear.