SC-41930 inhibits neutrophil infiltration of the cavine dermis induced by 12(R)-hydroxyeicosatetraenoic acid.
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.
Fretland
D J
DJ
Gastrointestinal Diseases Research Department, G. D. Searle and Co., Skokie, Illinois 60077.
Widomski
D L
DL
Shone
R L
RL
Penning
T D
TD
Miyashiro
J M
JM
Djuric
S W
SW
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006168:Guinea Pigs; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007271:Injections, Intradermal; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D009195:Peroxidase / Q000032:analysis / Q000378:metabolism; D012867:Skin / Q000166:cytology* / Q000187:drug effects
D001578:Benzopyrans; D006893:Hydroxyeicosatetraenoic Acids; C059950:SC 41930; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D009195:Peroxidase