Effect of Lonapalene on Metabolism of Exogenous Arachidonic Acid in Human Platelets
Coloma Gibert, Luı́s Vila, L. Puig, Josep Solà, J. M. de Moragas
Abstract
Coloma Gibert, Luı́s Vila, L. Puig, Josep Solà, J. M. de Moragas
Abstract
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.
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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.
Key concepts: Arachidonic acid, Arachidonic acid metabolism, Cyclooxygenase, Lipoxygenase, Platelet, Metabolism, Chemistry, Pharmacology