HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Actions of a 5-lipoxygenase inhibitor, Sch 40120, on acute inflammatory responses.

Abstract
Sch 40120 (10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b] [1,8]naphthyridin-5(7H)-one) is an inhibitor of the 5-lipoxygenase enzyme in rat neutrophils, human neutrophils and the the MC9 murine mast cell clone with IC50 values of 8, 4 and 7 microM, respectively. The drug was examined for its effects on acute inflammatory responses in the paw and pleural cavity of rats. The drug suppressed paw inflammation triggered by a reverse passive Arthus reaction or a subplantar injection of the polysaccharide carrageenan with p.o. ED50 values of 0.2 and 1.5 mg/kg, respectively. In reverse passive Arthus reaction and carrageenan pleurisy models, Sch 40120 was found to suppress both the cellular and fluid components of the acute inflammation. The p.o. ED50 values for inhibition of cells and fluid in pleurisy models were in the range of 0.1 to 0.7 mg/kg. When applied locally to the ears of mice, the drug blocked an arachidonic acid-induced and leukotriene-mediated ear inflammation with an ED50 of 0.072 mg/ear. These findings suggest that Sch 40120 is a potent anti-inflammatory agent that may be particularly useful in the treatment of inflammatory diseases such as psoriasis in which leukotrienes appear to be major mediators of the pathological symptoms that characterize the disease state.
AuthorsS R Smith, A W Watnick, R W Bryant, M Billah, M I Siegel
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 262 Issue 2 Pg. 721-8 (Aug 1992) ISSN: 0022-3565 [Print] United States
PMID1386887 (Publication Type: Journal Article)
Chemical References
  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Hydroxyeicosatetraenoic Acids
  • Lipoxygenase Inhibitors
  • Naphthyridines
  • Sch 40120
  • 5-hydroxy-6,8,11,14-eicosatetraenoic acid
Topics
  • Acute Disease
  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
  • Arthus Reaction (chemically induced)
  • Cyclooxygenase Inhibitors (pharmacology)
  • Humans
  • Hydroxyeicosatetraenoic Acids (biosynthesis)
  • In Vitro Techniques
  • Inflammation (drug therapy)
  • Lipoxygenase Inhibitors (pharmacology)
  • Naphthyridines (pharmacology)
  • Neutrophils (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: