Effects of Quinotolast, a New Orally Active Antiallergic Drug, on Experimental Allergic Models

• Published in: Japanese Journal of Pharmacology 1993, Vol.63(1), pp.73-81
• Main Authors: Kobayashi, Katsumasa, Hiroi, Jun, Kishi, Shinichi, Sawase, Kumi, Hirayama, Yoshitaka, Chihara, Satomi, Imai, Takumi, Shigi, Yasutaka, Shimomura, Kyoichi, Kohsaka, Masanobu
• Format: Article
• Language: English
• Subjects: Administration, Oral; Anaphylaxis - drug therapy; Animals; Antiallergics; Biological and medical sciences; Bronchoconstriction - drug effects; Cells, Cultured; Cromolyn Sodium - administration & dosage; Cromolyn Sodium - therapeutic use; Disease Models, Animal; Guinea Pigs; Histamine and antagonists. Allergy; Histamine Antagonists - administration & dosage; Histamine Antagonists - therapeutic use; Histamine Release - drug effects; Hypersensitivity - drug therapy; Leukotrienes - metabolism; Male; Mast Cells - cytology; Mast Cells - drug effects; Mediator release inhibitor; Medical sciences; Passive Cutaneous Anaphylaxis - drug effects; Pharmacology. Drug treatments; Quinolizines - administration & dosage; Quinolizines - pharmacology; Quinolizines - therapeutic use; Quinotolast; Rats; Rats, Sprague-Dawley; Tetrazoles - administration & dosage; Tetrazoles - pharmacology; Tetrazoles - therapeutic use
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.63.73

The effects of a new antiallergic drug, quinotolast [sodium 5-(4-oxo-1-phenoxy-4H-quinolizine-3-carboxamido)tetrazolate monohydrate], were studied and compared with those of tranilast, amlexanox, pemirolast, repirinast and disodium cromoglycate (DSCG) in experimental allergic models. Quinotolast potently inhibited such type I allergic reactions as passive cutaneous anaphylaxis (PCA) and anaphylactic bronchoconstriction in rats by both intravenous and oral dosing. All of these effects were stronger than those of the reference drugs tested. Quinotolast inhibited histamine release from rat peritoneal cells, but it had no antagonistic effect on histamine-, serotonin-, platelet activating factor- or bradykinin-induced cutaneous reactions in rats. Moreover, it was clearly demonstrated that quinotolast and DSCG had a cross tachyphylaxis to inhibit PCA in rats, suggesting that these drugs, at least in part, share the same mechanism of action. Furthermore, quinotolast potently inhibited PCA in guinea pigs in which DSCG and other reference drugs showed poor inhibitory activity. Quinotolast also showed stronger inhibitory effects on histamine and peptide leukotrienes release from guinea pig lung fragments or mouse cultured mast cells than the other drugs tested. Thus, the effect of quinotolast on type I allergic reaction would seem to be based on an inhibition of mediator release from inflammatory cells including mast cells. The results suggest that quinotolast will be beneficial in the treatment of type I allergy-related diseases.