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

• Published in: Prostaglandins, leukotrienes and essential fatty acids Vol. 38; no. 3; pp. 169 - 172
• Main Authors: Fretland, D.J., Widomski, D.L., Shone, R.L., Penning, T.D., Miyashiro, J.M., Djuric, S.W.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.12.1989; Elsevier
• Subjects: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Benzopyrans - pharmacology; Biological and medical sciences; Chemotaxis, Leukocyte - drug effects; Guinea Pigs; Hydroxyeicosatetraenoic Acids - pharmacology; In Vitro Techniques; Injections, Intradermal; Male; Medical sciences; Neutrophils - drug effects; Peroxidase - analysis; Peroxidase - metabolism; Pharmacology. Drug treatments; Skin - cytology; Skin - drug effects; Skin, nail, hair, dermoskeleton; Arachidonic acid derivatives; Rodentia; Granulocyte; Chemotaxis; Vertebrata; Mammalia; Guinea pig; Leukotriene B4; Neutrophile; Animal; Skin; Antagonist; Biological receptor
• ISSN: 0952-3278; 1532-2823
• DOI: 10.1016/0952-3278(89)90067-7

Psoriasis is a disease state characterized by epidermal proliferation, neutrophil infiltration, along with release of the proinflammatory mediators leukotriene-B 4 (LTB 4) and 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE]. LTB 4 and 12(R)-HETE are chemoattractant to the neutrophil, the latter approximately 1000X less potent. LTB 4 and 12(R)-HETE are present in psoriatic scale, the latter in quantities so much greater than LTB 4 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 μgm 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 ED 50 value of 13.5 mg/kg. Compounds such as SC-41930 may well have utility for treating human psoriasis.