Open AccessPotent inhibitory activity of HSR-6071, a new antiallergic agent, on Passive Cutaneous Anaphylaxis(PCA).
Author(s) -
Eiichi Makino,
Takuma Ohashi,
Hiromi Takahashi,
Hideo Kobayashi,
Yasuo Ito,
Hiroichi Nagai,
Akihide Koda,
Hiroshi Azuma
Publication year - 1990
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.52.87
Subject(s) - histamine , pharmacology , acetylcholine , chemistry , serotonin , bradykinin , ed50 , inhibitory postsynaptic potential , anaphylaxis , compound 48/80 , allergy , degranulation , immunology , endocrinology , biology , biochemistry , in vitro , receptor
Antiallergic effects of 6-(1-pyrrolidinyl)-N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamide (HSR-6071), a newly synthesized agent, were investigated. The 48-hr homologous passive cutaneous anaphylaxis (PCA) in rats was inhibited in a dose-dependent manner by i.v. and p.o. administration of the agent (ED50 = 0.0096 mg/kg and 0.18 mg/kg, respectively). The IgE-mediated histamine release from rat peritoneal exudate cells was inhibited by HSR-6071, with an IC50 of 4.6 x 10(-10) M. Regarding the non-immunological histamine release, HSR-6071 inhibited compound 48/80-induced, but not A23187-induced and spontaneous histamine release. On the other hand, an increase in vascular permeability induced by histamine, serotonin and bradykinin was unaffected by HSR-6071 in doses sufficient to inhibit PCA. In addition, the contractile responses of isolated guinea pig ileum to histamine, acetylcholine and serotonin were also unaffected by the agent even in a high concentration of 10(-4) M. These results indicate that HSR-6071 possesses a potent antiallergic activity and that the inhibition of PCA by HSR-6071 may be due to the suppression of chemical mediators release from mast cells.