Effect of thromboxane A2 (TXA2) synthase inhibitor and TXA2 receptor antagonist alone and in combination on antigen-induced bronchoconstriction in guinea pigs.
Thromboxane A2 (TXA2) causes bronchoconstriction and bronchial hyperresponsiveness. Two types of TXA2 modifiers, one synthase inhibitor and one receptor antagonist, are widely used for the treatment of asthma in Japan. Although the target of TXA2 modifiers is to inhibit bioactivity of TXA2, the pharmacological properties are somewhat different between these drugs. We studied the inhibitory effects of the TXA2 synthase inhibitor CS-518 and the TXA2 receptor antagonist S-1452 alone and in combination on antigen-induced bronchoconstriction in passively sensitized guinea pigs treated with diphenhydramine. Both CS-518 and S-1452 inhibited the antigen-induced bronchoconstriction dose-dependently with the plateau. The combination of these drugs at the maximal inhibitory doses did not have any more effect compared with each single dosing. The combination at the submaximal doses tended to show an additive effect, but the effect was not significant. These findings suggest that other prostanoids such as PGE2, PGI2, PGD2 and PGF2alpha may not take an important role in the antiasthmatic effects of TXA2 modifiers.
Yoshimi
Y
Y
The Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
Fujimura
M
M
Myou
S
S
Tachibana
H
H
Hirose
T
T
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013876:Thiophenes / Q000494:pharmacology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D000941:Antigens; D001643:Bridged Bicyclo Compounds; D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D008689:Methacrylates; D017482:Receptors, Thromboxane; D013876:Thiophenes; C056566:S 145; C055806:RS 5186; D013930:Thromboxane-A Synthase; C034364:ozagrel