The effect of a novel thromboxane A2 (TXA2) receptor antagonist (S-1452) on the antigen-induced bronchoconstriction and airway hyperresponsiveness in guinea pigs.
The effect of a novel thromboxane A2 (TXA2) receptor antagonist (S-1452) on antigen-induced bronchoconstriction and airway hyperresponsiveness in guinea pigs was studied. Ketotifen was used as a reference drug. S-1452 at doses of 1 and 3 mg/kg (per oral administration, 1 h before the injection of U-46619) clearly inhibited U-46619-induced pulmonary pressure increase. Ketotifen at a dose of 10 mg/kg did not affect U-46619-induced bronchoconstriction. S-1452 at doses of 3 and 10 mg/kg and ketotifen at a dose of 10 mg/kg inhibited the antigen-induced bronchoconstriction in guinea pigs which had been passively sensitized with guinea pig IgE antibody. S-1452 at a dose of 10 mg/kg inhibited repeated antigen provocation-induced airway hyperresponsiveness in guinea pigs. The accumulation of inflammatory cells by antigen provocation in bronchial alveolar lavage fluid (BALF) was inhibited by ketotifen but not by S-1452. These results indicate the efficacy of S-1452 on antigen-induced bronchoconstriction and antigen-induced airway hyperresponsiveness in guinea pigs.
Nagai
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Arimura
A
A
Yoshitake
K
K
Iwama
T
T
Sakurai
T
T
Koda
A
A
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006168:Guinea Pigs; D006969:Hypersensitivity, Immediate / Q000188:drug therapy*; D007073:Immunoglobulin E / Q000276:immunology; D007665:Ketotifen / Q000494:pharmacology; D010400:Penicillin G / Q000031:analogs & derivatives / Q000276:immunology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D012137:Respiratory System / Q000276:immunology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D005719:gamma-Globulins / Q000276:immunology
D044482:Benzeneacetamides; D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D011450:Prostaglandin Endoperoxides, Synthetic; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; C081938:benzylpenicilloyl-bovine-gamma-globulin; D005719:gamma-Globulins; C056566:S 145; D007073:Immunoglobulin E; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine; D010400:Penicillin G; D007665:Ketotifen