Pharmacological actions of Y-24180: I. A potent and specific antagonist of platelet-activating factor

Prostaglandins
M TerasawaT Tahara

Abstract

The ability of Y-24180, 4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]- 6,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a] [1,4]diazepine to inhibit platelet-activating factor (PAF)-induced reactions was investigated. Y-24180 (0.0003-0.003 mg/kg, i.v.) dose-dependently inhibited PAF-induced bronchoconstriction in guinea pigs, but even at a high dose of 10 mg/kg, i.v., it was either inactive or weakly active against the bronchoconstriction induced by histamine, serotonin, acetylcholine, arachidonic acid, bradykinin, or leukotriene D4. Oral doses (0.003-0.1 mg/kg) of Y-24180 also prevented hemoconcentration due to PAF in a dose dependent manner and produced a parallel shift of the PAF dose-response curve. Y-24180 (0.0003-0.1 mg/kg, i.v.) and WEB 2086 (0.03-1 mg/kg, i.v.) dose-dependently reversed PAF-induced hypotension in anesthetized rats. In mice, PAF-induced lethality was inhibited by Y-24180 and WEB 2086 with ED50 values of 0.022 and 1.42 mg/kg, p.o., and 0.023 and 0.12 mg/kg, i.v., respectively. This protective effect of Y-24180 given p.o. persisted for at least 6 hr. In actively sensitized mice lethal anaphylactic shock was prevented by oral doses of Y-24180 and WEB 2086 with ED50 values of 0.095 and 0.69 mg/kg, respect...Continue Reading

References

Aug 1, 1987·Agents and Actions·R P CarlsonJ Chang
Mar 1, 1988·Prostaglandins·A K MyersP Ramwell
May 1, 1987·Chemical & Pharmaceutical Bulletin·T TaharaY Maruyama
Aug 1, 1987·Japanese Journal of Pharmacology·M TerasawaY Maruyama
Feb 1, 1985·Nursing·M R Cohen
Feb 1, 1985·The Journal of Allergy and Clinical Immunology·A L Sheffer
Feb 26, 1985·European Journal of Pharmacology·Z TerashitaS Sumida
Apr 25, 1983·Life Sciences·Z TerashitaK Nishikawa
Jun 1, 1983·British Journal of Pharmacology·A MyersP Ramwell
Jan 1, 1981·Annals of the New York Academy of Sciences·B B VargaftigF Wal

❮ Previous
Next ❯

Citations

Jan 1, 1995·Journal of Lipid Mediators and Cell Signalling·M SaitoT Matsuda
Apr 15, 1996·Environmental Toxicology and Pharmacology·H KomatsuT Okumoto
Dec 9, 2003·Life Sciences·Yu-Ying Chao, Chung-Ren Jan
Jul 30, 2002·European Journal of Pharmacology·Naoki InagakiHiroichi Nagai
Jun 1, 1997·Journal of Lipid Mediators and Cell Signalling·H Le SolleuJ P Dubost
Dec 17, 2009·The Journal of Biological Chemistry·Nobuaki HirotaMotonao Nakamura
Jan 22, 2005·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Chung-Ren Jan, Yu-Ying Chao

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anaphylaxis

Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death.