title: The in vitro 5-lipoxygenase and cyclo-oxygenase inhibitor L-652,343 does not inhibit 5-lipoxygenase in vivo in human skin.
abstract: 1 3-hydroxy-5-trifluoromethyl-N-[2-(2-thienyl)-2-phenyl-ethenyl]-benzo(B) thiophene-2-carboxamide (L-652,343) is a 5-lipoxygenase and cyclo-oxygenase inhibitor in vitro. 2 In psoriasis increased concentrations of arachidonic acid transformation products are found in the lesional skin which may be important in the pathogenesis of the disease. We have measured the effect of orally administered L-652,343 on the concentration of LTB4 and prostaglandins in the lesional skin. 3 Eight patients with stable chronic plaque psoriasis received 500 and 250 mg of L-652,343, 12 h apart. A chamber technique was used to collect skin exudate samples from abraded plaques before and at 4, 24 and 48 h after the first dose. Exudates were analysed for LTB4 by a neutrophil chemokinesis assay and for PGE2 and PGD2 by RIA. 4 PGE2 and PGD2 levels were significantly reduced at 4 and 24 h after the first dose of L-652,343 but LTB4 levels were not affected indicating inhibition of the cyclo-oxygenase pathway but not of the 5-lipoxygenase pathway. This shows the importance of confirming that the action of 5-lipoxygenase inhibiting drugs in vitro occurs in vivo.
authors.affiliation: Institute of Dermatology, United Medical School, Guys Hospital, London.
authors.forename: R M
authors.initials: RM
authors.lastname: Barr
authors.forename: A K
authors.initials: AK
authors.lastname: Black
authors.forename: P M
authors.initials: PM
authors.lastname: Dowd
authors.forename: O
authors.initials: O
authors.lastname: Koro
authors.forename: K
authors.initials: K
authors.lastname: Mistry
authors.forename: J L
authors.initials: JL
authors.lastname: Isaacs
authors.forename: M W
authors.initials: MW
authors.lastname: Greaves
mesh_terms: D000328:Adult; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008297:Male; D008875:Middle Aged; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism; D011565:Psoriasis / Q000201:enzymology / Q000378:metabolism; D012867:Skin / Q000201:enzymology* / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011457:Prostaglandins D; D011458:Prostaglandins E; D013876:Thiophenes; C051277:L 652343; D007975:Leukotriene B4; D001091:Arachidonate Lipoxygenases; D015232:Dinoprostone; D015230:Prostaglandin D2