Potent inhibitory activity of HSR-6071, a new antiallergic agent, on passive cutaneous anaphylaxis (PCA).
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.
Makino
E
E
Central Research Laboratories, Hokuriku Seiyaku Co., Ltd., Fukui, Japan.
Ohashi
T
T
Takahashi
H
H
Kato
H
H
Ito
Y
Y
Nagai
H
H
Koda
A
A
Azuma
H
H
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000276:immunology; D001200:Ascaris / Q000276:immunology; D001393:Azoles / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000494:pharmacology; D004140:Dinitrophenols / Q000276:immunology; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D007073:Immunoglobulin E / Q000276:immunology; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D013189:SRS-A / Q000037:antagonists & inhibitors; D013777:Tetrazoles / Q000494:pharmacology*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000631:Aminopyridines; D000941:Antigens; D001393:Azoles; D004140:Dinitrophenols; D011759:Pyrrolidines; D013189:SRS-A; D013777:Tetrazoles; C063147:HSR 6071; D007073:Immunoglobulin E; D000001:Calcimycin; D003189:p-Methoxy-N-methylphenethylamine; C045742:amlexanox; D004205:Cromolyn Sodium; D007665:Ketotifen