Effect of 8-hexyloxy-3-(1H-tetrazol-5-yl)-2H-chromen-2-one [KP-136] on experimental asthma: a comparison with disodium cromoglycate.
The pharmacological properties of 8-hexyloxy-3-(1H-tetrazol-5-yl)-2H-chromen-2-one, KP-136 were compared with those of an antiallergic medicament, disodium cromoglycate (DSCG) in experimental asthma models. KP-136 (0.125-1 mg/kg i.v., 0.5-2 mg/kg p.o.) produced a dose-dependent inhibition to allergic asthma of rats and was more potent than DSCG (1-5 mg/kg i.v.). KP-136 (1 mg/kg, i.v.) was also effective on allergic asthma of guinea pigs, although DSCG was ineffective even at a high dose of 50 mg/kg (i.v.). In rats, both KP-136 and DSCG significantly blocked the reduction of histamine content of the trachea after allergic asthma and inhibited the antigen-induced histamine release from lung fragments (KP-136 0.5 micrograms/ml, DSCG 50 micrograms/ml) and peritoneal exudate cells (KP-136 0.1 micrograms/ml, DSCG 10 micrograms/ml). KP-136 also showed relaxation activity for isolated guinea pig trachea at high doses of 2 and 5 micrograms/ml. The major mechanism of the potent antiasthmatic activity of KP-136 is postulated to be the blocking of bronchoactive mediator release. The relaxation of smooth muscle is also suggested to be an additive mechanism.
Kuriyama
K
K
Kyoto Research Laboratories, Kaken Pharmaceutical Co. Ltd., Kyoto, Japan.
Hiyama
Y
Y
Ito
K
K
D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D002199:Capillary Permeability; D002867:Chromones / Q000494:pharmacology / Q000627:therapeutic use*; D004205:Cromolyn Sodium / Q000627:therapeutic use*; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006636:Histamine Release / Q000187:drug effects; D007106:Immune Sera / Q000276:immunology; D009126:Muscle Relaxation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013777:Tetrazoles; D014132:Trachea / Q000503:physiopathology
D000941:Antigens; D002867:Chromones; D006634:Histamine H1 Antagonists; D007106:Immune Sera; D013777:Tetrazoles; C053066:KP 136; D006632:Histamine; D004205:Cromolyn Sodium