Study on anti-SRS drugs

Abstract

There are many evidences to indicate that slow reacting substance of anaphylaxis (SRS-A) plays a role as a bronchoconstrictor in allergic asthmatic attacks. In the present paper, effects of 3-isobutyryl-2-isopropylpyrazolo [1,5-a]pyridine(KC-404), 2-methyl-3-piperidino-β-propionaphtone hydrochlo-ride(KZ-) and FPL-55712 on experimentally-caused allergic reactions were investigated. 1) 48 hr homologous passive cutaneous anaphylaxis(PCA) in rats was clearly inhibited by p.o. or i.v. administration of KC-404 and KZ-lll, while FPL-55712 inhibited the PCA only by i.v. administration. 2) All drugs except for 10−4 g/ml of KZ-lll neither inhibited antigen-induced histamine release from sensitized rat peritoneal mast cells nor generation of SRS from rat polymorphonuclear leukocytes induced by calcium ionophore A 23187. The ionophore-induced histamine release from rat peritoneal mast cells was not inhibited by any of the drugs. 3) KC-404 and KZ-111 in concentrations of 10−6to 10−5 g/ml produced a downward displacement of leukotriene D4(LTD4)-induced maximum contraction of guinea pig ileum and tracheal muscle in the concentration-response curves. On the other hand, 10−6 g/ml FPL-55712 shifted parallel the concentration-response curves to the right in both smooth muscle preparations. 4) Each 50 % inhibitory concentration of the three drugs to the contraction of ileum by LTD4 was lower than that to histamine, prostaglandin F2α or BaCl2- 5) KC-404 and KZ-111 inhibited CaCl2-induced contraction of ileum depolarized with high-K+, but FPL-55712 had no effect on the contraction. 6) All drugs inhibited the Schultz-Dale reaction in guinea pig tracheal muscle. 7) Respiratory disorders seen in the case of experimental asthma in guinea pigs were inhibited by KC-404 and KZ-111 given p.o., but not by FPL-55712.