LG 30435, a new potential antiasthmatic agent

ABSTRACT: LG 30435 l ~ a new quaternary phenothiazine derivative with H1-antihistaminlc and antlmuscarinlc properties. The ability of LG 30435 to prevent changes in respiratory mechanics, Induced by different mediators and the Immunological reaction, was monitored together with biological and radiolmmunological determination of circulating thromboxane-A1 (fxA1) In anaesthetized guinea-pigs. LG 30435 dose-de-pendently reduces the bronchocon!;trlctlon and TxA1 generation caused by different stimuli such as histamine, acetylcholine, leukntriene c. (L TC.) and PAF-acether. In addition i.v. and aerosol administration of LG 30435 causes a dose-dependent reduct ion of the Increase In ain\•ay resistance and TxA1 generation Induced by ovalbumin challenge In actively sensitized animals. LG 30435 Infused at different concentrations through the Isolated guinea-pig lu ngs Inhibits the TxD1 generation caused by different anaphylactic mediators, but not by arachidonic acid. These data, which further substantiate the bronchodilator activity of LG 30435 against a variety of stimuli and demonstrate Its protective properties on lung anaphylaxl~, suggest that this compound has a potential therapeutic value In the treatment of asthma