Tazanolast (TO 188)

Tazanolast is a selective mast-cell-stabilizing drug, on ozone-induced airway hyperresponsiveness in guinea pigs.

Tazanolast, an orally active mast-cell-stabilizing drug, which has been shown to suppress passive cutaneous anaphylaxis, Schultz-Dale reaction in isolated tracheal muscle, and experimental asthma without antagonistic actions upon histamine- and leukotriene-D4-induced contraction, IgE-mediated or compound 48/80-induced histamine release from mast cells and lung fragments, compound 48/80-induced Ca2+ uptake into mast cells from extracellular medium, compound 48/80-induced translocation of protein kinase C from the cytosol to the membrane fraction of mast cells, and inositol trisphosphate production without directly inhibiting phospholipase C in mast cells[1].

Tazanolast administered before ozone exposure at doses of 30, 100, or 300 mg/kg inhibits ozone-induced airway hyperresponsiveness in a dose-dependent manner. Tazanolast administered after ozone exposure does not inhibit the airway hyperresponsiveness. Tazanolast does not significantly change the cell distribution of bronchoalveolar lavage (BAL) cells at 2 h after the exposure. Tazanolast significantly inhibits ozone-induced airway hyperresponsiveness in guinea pigs[1].

[1]. Igarashi A, et al. Tazanolast inhibits ozone-induced airway hyperresponsiveness in guinea pigs. Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1531-5.