Pulmonary aerosol actions of LY188695 (KB2413), a new potent H1-receptor antagonist

The new potent H₁ receptor antagonist, LY188695 (KB2413), was delivered to guinea pigs as a pulmonary aerosol and its ability to inhibit histamine-induced airway obstruction examined. Aerosol LY188695 was more effective than inhaled chlorpheniramine or clemastine in reducing the pulmonary gas trapping produced by histamine challenge. Lung antihistamine effects occurred within minutes of a brief, low concentration aerosol exposure and persisted for at least 1 hour. LY188695 aerosol treatment did not produce significant inhibition of methacholine-induced gas trapping. Although systemic antihistamine effects occurred 50 minutes after LY188695 inhalation, aerosol administration produced an enhanced local (i.e., lung) action compared to intravenous delivery.