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The KCNQ potassium channels are neuronal modulators which combine with other KQT or KCNE channels to form heteromultimers. XE 991 is a blocker of KCNQ channels that potently inhibits KCNQ1 and 2 homomeric channels (IC50 = 0.75 and 0.71 μM, respectively) as well as KCNQ2+3 heteromultimers (IC50 = 0.6 μM).[1] It much less effectively blocks eag, erg, and elk channels. The effectiveness of XE 991 against KCNQ channels depends on partners or accessory proteins.[2] Through these actions, XE 991 enhances acetylcholine release from rat brain slices (EC50 = 490 nM) and shows good in vivo potency and duration of action, suggesting utility in Alzheimer’s disease therapeutics.[3] While early studies focused on actions in the central nervous system, XE 991 can be used to explore the roles of KCNQ channels in neuronal regulation throughout the body.[4]

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