SC-41930 inhibits neutrophil infiltration of the cavine dermis induced by 12(R)-hydroxyeicosatetraenoic acid.

Abstract

Psoriasis is a disease state characterized by epidermal proliferation, neutrophil infiltration, along with release of the proinflammatory mediators leukotriene-B4 (LTB4) and 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE]. LTB4 and 12(R)-HETE are chemoattractant to the neutrophil, the latter approximately 1000X less potent. LTB4 and 12(R)-HETE are present in psoriatic scale, the latter in quantities so much greater than LTB4 that it is proposed as a primary mediator of neutrophil infiltration in psoriasis. 12(R)-HETE, synthesized in optically pure form by a new, shorter route, was injected into the cavine dermis. At a dose of 25 micrograms m per intradermal site, 12(R)-HETE was a significant chemoattractant to the neutrophil (as assessed by dermal myeloperoxidase levels). SC-41930, 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)-propoxy]- 3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid, given intragastrically inhibited 12(R)-HETE-induced neutrophil infiltration of the cavine dermis with an ED50 value of 13.5 mg/kg. Compounds such as SC-41930 may well have utility for treating human psoriasis.

• Authors: D J Fretland, D L Widomski, R L Shone, T D Penning, J M Miyashiro, S W Djuric
• Journal: Prostaglandins, leukotrienes, and essential fatty acids (Prostaglandins Leukot Essent Fatty Acids) Vol. 38 Issue 3 Pg. 169-72 (Dec 1989) ISSN: 0952-3278 [Print] Scotland
• PMID: 2560200 (Publication Type: Journal Article)

Chemical References

• Benzopyrans
• Hydroxyeicosatetraenoic Acids
• SC 41930
• 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
• Peroxidase

Topics

• 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
• Animals
• Benzopyrans (pharmacology)
• Chemotaxis, Leukocyte (drug effects)
• Guinea Pigs
• Hydroxyeicosatetraenoic Acids (pharmacology)
• In Vitro Techniques
• Injections, Intradermal
• Male
• Neutrophils (drug effects)
• Peroxidase (analysis, metabolism)
• Skin (cytology, drug effects)