Recently, it has been shown that the dual enkephalinase inhibitor PL37 effectively inhibited isosorbide dinitrate (ISDN)–induced cephalic mechanical hypersensitivity (MH) in rats. Here, we tested whether a combination of sumatriptan and PL37 would result in an additive or a synergistic effect. So, we used the rat ISDN model of migraine as sumatriptan have been shown to reduce cephalic MH in this model. After determination of sumatriptan and PL37 ED50, we showed, by isobolographic analysis, that the combination of increasing fractional increments of both drugs doses produced a synergistic effect. So, combining PL37 and sumatriptan may be a useful strategy for migraine management, as an alternative to patients unable to tolerate sumatriptan side effects or those that have not found pain relief in the existing pharmacopeia.
Learning Objectives:
Upon completion, participant will be able to demonstrate the interest of using combination of analgesics in migraine treatment
At the end of the training, the participant will be able to demonstrate the interest of targeting enkephalins in the treatment of migraine.
Upon completion, participant will be able to demonstrate the interest of using a dual enkephalinase inhibitor in association with sumatriptan
.jpg "Philippe Luccarini, PhD photo")