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Pharmacologic and clinical effects of lonapalene (RS 43179), a 5-lipoxygenase inhibitor, in psoriasis.

Abstract
The pharmacologic and clinical effects of the 5-lipoxygenase inhibitor, lonapalene, have been determined in a double-blind, placebo-controlled, topical study in ten volunteers with psoriasis. A statistically significant clinical improvement was seen in lesions treated with 2% lonapalene ointment as compared with vehicle-treated sites. Although there was a statistically significant reduction in the levels of material similar or identical to the chemoattractant arachidonate 5-lipoxygenase product, leukotriene B4, in skin chamber fluid samples from lonapalene versus vehicle treated lesions, no significant reduction in arachidonic acid or 12-hydroxy-5,8,10,14-eicosatetraenoic acid was seen. The reduction in leukotriene B4 equivalents occurred before significant clinical improvement in lesions was seen. This and the selectivity of the pharmacologic response suggest that the therapeutic effect of topical lonapalene in psoriasis might be related to inhibition of leukotriene B4 synthesis. These results support the view that 5-lipoxygenase inhibitors may be useful in the treatment of psoriasis, and that leukotriene B4 is a relevant mediator of the pathology of this disease.
AuthorsA K Black, R D Camp, A I Mallet, F M Cunningham, M Hofbauer, M W Greaves
JournalThe Journal of investigative dermatology (J Invest Dermatol) Vol. 95 Issue 1 Pg. 50-4 (Jul 1990) ISSN: 0022-202X [Print] United States
PMID2164070 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Arachidonic Acids
  • Hydroxyeicosatetraenoic Acids
  • Lipoxygenase Inhibitors
  • Naphthalenes
  • Leukotriene B4
  • Arachidonic Acid
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • RS 43179
  • Arachidonate Lipoxygenases
Topics
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • Adult
  • Arachidonate Lipoxygenases (antagonists & inhibitors)
  • Arachidonic Acid
  • Arachidonic Acids (metabolism)
  • Chromatography, High Pressure Liquid
  • Clinical Trials as Topic
  • Double-Blind Method
  • Female
  • Humans
  • Hydroxyeicosatetraenoic Acids (metabolism)
  • Leukotriene B4 (metabolism)
  • Lipoxygenase Inhibitors
  • Male
  • Middle Aged
  • Naphthalenes (therapeutic use)
  • Psoriasis (drug therapy, metabolism, physiopathology)

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