Effect of lonapalene on metabolism of exogenous arachidonic acid in human platelets.
Lonapalene was studied as a topical antipsoriatic agent on the basis of its inhibitory effect on 5-lipoxygenase. We studied the effect of lonapalene on the metabolism of exogenous arachidonic acid in washed platelet suspensions by RP-HPLC. Lonapalene was shown to inhibit platelet cyclooxygenase, with substrate diversion towards 12-HETE production. The pattern of inhibition was similar to that of indometacin, although lonapalene was about 1,000 times weaker. The dual inhibition of lonapalene and concomitant deviation of arachidonic acid metabolism may have potential implications, with regard to therapeutic indications and side effects, which deserve further study.
Gibert
C
C
Unitat de Recerca Biomédica (Eicosanoids Laboratory), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Vila
L
L
Puig
L
L
Solá
J
J
Moragas
J M
JM
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D015777:Eicosanoids / Q000096:biosynthesis; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D066298:In Vitro Techniques; D008084:Lipoxygenase / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D001095:Arachidonic Acids; D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; D009281:Naphthalenes; D016718:Arachidonic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C045954:RS 43179; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases