HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Antiinflammatory effects of second-generation leukotriene B4 receptor antagonist, SC-53228: impact upon leukotriene B4- and 12(R)-HETE-mediated events.

Abstract
Leukotriene B4 (LTB4) and 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE] are proinflammatory products of arachidonic acid metabolism that have been implicated as mediators in a number of inflammatory diseases. When injected intradermally into the guinea pig. LTB4 and 12(R)-HETE elicit a dose-dependent migration (chemotaxis) of neutrophils (PMNs) into the injection sites as assessed by the presence of a neutrophil marker enzyme myeloperoxidase. SC-41930 (7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxyl]-3,4-dihy dro-8-propyl-2H - 1-benzopyran-2-carboxylic acid), a first-generation LTB4 receptor antagonist, inhibited the chemotactic actions of LTB4 when given orally with an ED50 value of 1.7 mg/kg. The second-generation LTB4 receptor antagonist, SC-53228 [(+)-(S)-7-(3-(2-(cyclopropylmethyl)-3-methoxy-4- [(methylamino)carbonyl]phenoxy)propoxy)-3,4-dihydro-8-propyl-2H-1- benzopyran-2-propanoic acid], inhibited LTB4-induced chemotaxis when given intragastrically with an ED50 value of 0.07 mg/kg. Furthermore, SC-53228 inhibited 12(R)-HETE-induced granulocyte chemotaxis with an oral ED50 value of 5.8 mg/kg. When dosed orally over a range of 0.03-100 mg/kg, SC-53228 gave Cmax plasma concentrations of 0.015-41.1 micrograms/ml. SC-53228 inhibited LTB4-primed membrane depolarization of human neutrophils with an IC50 value of 34 nM. As a potent LTB4 receptor antagonist, SC-53228 may well have application in the medical management of disease states such as asthma, rheumatoid arthritis, inflammatory bowel disease, contact dermatitis, and psoriasis, in which LTB4 and/or 12(R)-HETE are implicated as inflammatory mediators.
AuthorsD J Fretland, C P Anglin, M Bremer, P Isakson, D L Widomski, S K Paulson, S H Docter, S W Djuric, T D Penning, S Yu
JournalInflammation (Inflammation) Vol. 19 Issue 2 Pg. 193-205 (Apr 1995) ISSN: 0360-3997 [Print] UNITED STATES
PMID7601505 (Publication Type: Journal Article)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzamides
  • Benzopyrans
  • Biomarkers
  • Hydroxyeicosatetraenoic Acids
  • Receptors, Leukotriene B4
  • SC 41930
  • 7-(3-(2-(cyclopropylmethyl)-3-methoxy-4-((methylamino)carbonyl)phenoxy)propoxy)-3,4-dihydro-8-propyl-2H-1-benzopyran-2-propanoic acid
  • Leukotriene B4
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • Peroxidase
Topics
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, pharmacology)
  • Benzamides (administration & dosage, pharmacology)
  • Benzopyrans (administration & dosage, pharmacology)
  • Biomarkers
  • Chemotaxis, Leukocyte (drug effects)
  • Granulocytes (drug effects)
  • Guinea Pigs
  • Hydroxyeicosatetraenoic Acids (administration & dosage, pharmacology)
  • Injections, Intradermal
  • Leukotriene B4 (administration & dosage, pharmacology)
  • Male
  • Membrane Potentials (drug effects)
  • Neutrophils (drug effects, enzymology)
  • Peroxidase (analysis)
  • Receptors, Leukotriene B4 (antagonists & inhibitors, physiology)
  • Skin (drug effects, immunology, pathology)

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 network!


Choose Username:
Email:
Password:
Verify Password: