LG 30435 is a new bronchodilator agent with multiple sites of action.
LG 30435, a new quaternary derivative of the H1-histamine antagonist mequitazine, was evaluated against bronchospasm induced by different agonists. This compound inhibited equipotently methacholine- and histamine-induced contractions of isolated guinea-pig trachea. When administered to guinea-pig by the i.v. and/or the aerosol route, LG 30435 inhibited dose dependently the bronchospasm induced by acetylcholine and histamine and to a lesser degree that induced by 5-hydroxytryptamine and LTD4. When compared to that of mequitazine, its potency was higher in each case, up to 500-fold when tested in vitro against methacholine. LG 30435 also counteracted antigen-induced bronchospasm both in passively sensitized guinea-pigs and in actively sensitized rats. This compound had a rapid onset of action and an adequate duration after aerosol administration. It was poorly absorbed both by the oral and the aerosol routes and it did not appear to penetrate the blood-brain barrier. These results show that LG 30435 is a new aerosol bronchodilator agent, which, due to its multiple pharmacodynamic actions and to its suitable pharmacokinetics, is potentially useful in the therapy of obstructive airways disease.
D000042:Absorption; D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000336:Aerosols; D000707:Anaphylaxis / Q000503:physiopathology; D000758:Anesthesia; D000818:Animals; D001993:Bronchodilator Agents / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D006633:Histamine Antagonists; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010095:Oxotremorine / Q000037:antagonists & inhibitors; D010640:Phenothiazines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D012702:Serotonin Antagonists; D014132:Trachea / Q000187:drug effects
D000336:Aerosols; D001993:Bronchodilator Agents; D006633:Histamine Antagonists; D010640:Phenothiazines; D012702:Serotonin Antagonists; C049967:LG 30435; D010095:Oxotremorine; D000109:Acetylcholine; C006069:mequitazine