Preview of Potential Therapeutic Applications of Leukotriene B4 Inhibitors in Dermatology

Abstract

This article reviews the mechanisms and potential therapeutic uses of compounds with inhibitory effects on leukotriene B4 (LTB4) production or its activity, and focuses on compounds that have been shown in animal and/or human studies to have potential efficacy in treating dermatological disorders. These compounds, many of which are not familiar to many dermatologists, include inhibitors of 5-lipoxygenase such as ETH615, 15-hydroxyeicosatetraenoic acid, leflunomide, linetastine, lonapalene, MK886, R-68151 and zileuton, and antagonists of LTB4 such as SC53228, SC50605, SC51146 and VML295. The purpose of this paper is to introduce our colleagues to these potentially useful compounds currently in preclinical or early clinical testing.

Photodistributed Lichenoid Drug Eruption with Rhabdomyolysis Occurring during Leflunomide Therapy

“…This drug has potential efficacy in treating dermatological disorders, because of its inhibitory effects on leukotriene B 4 production or its activity [7]. The most common adverse events reported in randomized double-blind, placebo-controlled trials in patients receiving leflunomide were diarrhea (27%), respiratory infections (21%), nausea (13%), headache (13%), rash (12%), increased serum hepatic aminotransferases (10%), dyspepsia (10%) and alopecia (9%).…”

Identification of 4-[4-(4-Fluoro-Phenyl)-Thiazol-2-Ylamino]-2,6-Dimethyl-Phenol (KR-33749) as an Inhibitor of 5-Lipoxygenase with Potent Antiinflammatory Activity

“…As leukotrienes are critical mediators of chronic inflammation, various approaches to interfere with the production or function of leukotrienes have been applied to develop drugs for inflammatory diseases, and possibly therapeutic intervention in LTB 4 formation will also be a promise for the treatment of inflammation-related skin disorders [21] , especially in cases that have corticosteroid insensitivity [22] . Currently, the only 5-LO inhibitor approved for oral application is zileuton for asthma therapy, but it has the disadvantage of having to take doses 4 times a day and causing other side effects [23] .…”

Gemeine Pestwurz (<i>Petasites hybridus</i>) – Portrait einer Arzneipflanze

“…synthetischen Leukotriensynthesehemmern bei chronischer Urticaria hin [25,26]. Auch bei Psoriasis wurden diverse Lipoxygenasehemmer topisch oder systemisch erfolgreich klinisch erprobt [27,28]. Die Zukunft wird zeigen, ob Pestwurzextrakt auch bei diesen Indikationen wirksam ist.…”