Inhibitory effect of NZ-107 on anaphylactic bronchoconstriction in guinea pigs and rats.
We studied the effect of NZ-107 in a number of animal models of anaphylactic bronchoconstriction. In conscious guinea pigs, pretreated with indomethacin, pyrilamine and propranolol, passively sensitized with heterologous anti serum, NZ-107 in doses of 10-30 mg/kg per os inhibited the aerosolized antigen-induced cough and collapse. NZ-107 in a high dose of 100 mg/kg per os significantly prevented aerosolized antigen-induced anaphylactic collapse, but not cough in actively or passively sensitized conscious guinea pigs and also significantly protected aerosolized histamine-induced collapse, but not cough in conscious guinea pigs. This compound had little inhibitory effect on aerosolized acetylcholine-induced cough and collapse. In anesthetized animals, the effect of NZ-107 on bronchoconstriction induced by intravenous administration of antigen and various agonists was examined by the method of Konzett and Rössler. In doses of 10-50 mg/kg per os, NZ-107 inhibited antigen-induced bronchoconstriction in anesthetized guinea pigs. NZ-107 when intravenously administered to the anesthetized guinea pigs inhibited not only leukotriene D4-induced bronchoconstriction, but also thromboxane A2 mimetic U-46619-, platelet-activating factor- and histamine-induced bronchoconstriction. In anesthetized rats, NZ-107 in a dose of 300 mg/kg per os tended to inhibit the antigen-induced bronchoconstriction, but this effect was not significant. These results indicate that NZ-107 acts as a spasmolytic agent which inhibits bronchial responses to antigens or various other bronchoconstrictors in animal models, suggesting that NZ-107 may be potentially beneficial in the treatment of bronchial asthma.
Iwama
T
T
Nissan Chemical Industries Ltd., Saitama, Japan.
Shikada
K
K
Yamamoto
A
A
Sakashita
M
M
Hibi
M
M
Tanaka
S
S
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine; D000707:Anaphylaxis / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine; D007213:Indomethacin; D007275:Injections, Intravenous; D008297:Male; D010047:Ovalbumin; D010972:Platelet Activating Factor; D011433:Propranolol; D011450:Prostaglandin Endoperoxides, Synthetic; D011724:Pyridazines / Q000494:pharmacology*; D011738:Pyrilamine; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis; D013189:SRS-A
D002867:Chromones; D010972:Platelet Activating Factor; D011450:Prostaglandin Endoperoxides, Synthetic; D011724:Pyridazines; D013189:SRS-A; C062698:NZ 107; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D006632:Histamine; C006312:FPL 55712; D010047:Ovalbumin; D011433:Propranolol; D011738:Pyrilamine; D000109:Acetylcholine; D007213:Indomethacin