Description
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 (IC
50 = 0.75 and 0.71 μM, respectively) as well as KCNQ2+3 heteromultimers (IC
50 = 0.6 μM). It much less effectively blocks eag, erg, and elk channels. The effectiveness of XE 991 against KCNQ channels depends on partners or accessory proteins. Through these actions, XE 991 enhances acetylcholine release from rat brain slices (EC
50 = 490 nM) and shows good
in vivo potency and duration of action, suggesting utility in Alzheimer’s disease therapeutics. 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.
Uses
XE 991 dihydrochloride is a potent & selective inhibitor of KCNQ voltage-gated K-channels.
References
[1] H S WANG. KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel.[J]. Science, 1998, 282 5395: 1890-1893. DOI:
10.1126/science.282.5395.1890[2] H S WANG. Molecular basis for differential sensitivity of KCNQ and I(Ks) channels to the cognitive enhancer XE991.[J]. Molecular Pharmacology, 2000, 57 6: 1218-1223.
[3] R ZACZEK. Two new potent neurotransmitter release enhancers, 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone and 10,10-bis(2-fluoro-4-pyridinylmethyl)-9(10H)-anthracenone: comparison to linopirdine.[J]. Journal of Pharmacology and Experimental Therapeutics, 1998, 285 2: 724-730.
[4] JOANNA M HAWRYLUK. KCNQ channels determine serotonergic modulation of ventral surface chemoreceptors and respiratory drive.[J]. Journal of Neuroscience, 2012, 32 47: 16943-16952. DOI:
10.1523/jneurosci.3043-12.2012
