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

Abstract

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.

Preclinical Efficacy of Emedastine, a Potent, Selective Histamine H1 Antagonist for Topical Ocular Use

“…Topical anti-histaminic activity was also observed following pulmonary aerosol delivery in guinea pigs. The compound was more effective than either chlorpheniramine or clemastine administered in similar fashion (10).…”

Methods, Measurements, and Interpretation of Animal Lung Function in Health and Disease

“…Furthermore, anesthetized animals are sometimes evaluated when breathing spontaneously or when paralyzed and artificially ventilated. Typically, breathing mechanics (C dyn and R) are assessed, although some investigators have used other indices, such as flow-derived parameters obtained from a forced expiratory volume maneuver (Holroyde et al, 1980), trapped gas in excised lungs (Wiester et al, 2005;Silbaugh et al, 1987), blood gas measurements (Wiester et al, 2005, or cough (Clay and Thompson, 1985). Forced oscillatory techniques used to measure frequencydependent changes in lung mechanics have becoming increasingly popular (Schuessler and Bates, 1995).…”