Antiallergic effects of 4-[2-oxo-3-(1H-tetrazol-5-yl)-2H-chromen-8-yloxy]-bu tyric acid.
Antiallergic effects of 4-[2-oxo-3-(1H-tetrazol-5-yl)-2H-chromen-8-yloxy]-buty ric acid (C4C) were studied. C4C is an active principal metabolite of an orally effective antiallergic agent, KP-136. C4C (0.2-1 mg/kg, i.v.) markedly inhibited the mast cell-mediated homologous PCA of rats and the experimental allergic asthma of rats and guinea pigs, although it had almost no effects on heterologous PCA and compound 48/80-induced cutaneous response in rats. C4C (0.2 mg/kg, i.v.) was scarcely effective on cutaneous responses induced by intradermal injection of histamine and serotonin which are principal chemical mediators of rat homologous PCA, and it blocked the decrease of skin histamine content after the PCA. In addition, C4C (0.01-0.5 micrograms/ml) inhibited the increase of 45Ca uptake of mast cells, the histamine release and the degranulation induced by the antigen-antibody interaction. These effects of C4C were much the same as those of KP-136. From the above findings, C4C is considered to be an antiallergic agent that inhibits the mast cell activation by blocking the calcium influx, and it shares similar pharmacological properties with KP-136.
Kuriyama
K
K
Central Research Laboratories, Kaken Pharmaceutical Co., Ltd., Kyoto, Japan.
Hiyama
Y
Y
Ito
K
K
D000818:Animals; D001200:Ascaris / Q000276:immunology; D001249:Asthma / Q000139:chemically induced / Q000517:prevention & control; D001393:Azoles / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D002867:Chromones / Q000494:pharmacology*; D004205:Cromolyn Sodium / Q000494:pharmacology; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D006967:Hypersensitivity / Q000188:drug therapy*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D013777:Tetrazoles / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects
D001393:Azoles; D002132:Calcium Radioisotopes; D002867:Chromones; D007166:Immunosuppressive Agents; D013777:Tetrazoles; C060809:4-(2-oxo-3-(1H-tetrazol-5-yl)-2H-chromen-8-yloxy)butyric acid; C053066:KP 136; D004205:Cromolyn Sodium; D002118:Calcium