XE 991 2HCl (dihydrochloride), a Kv7 (KCNQ) channels blocker, potently inhibits Kv7.1 (KCNQ1), Kv7.2 (KCNQ2), Kv7.2 + Kv7.3 (KCNQ3) channel, and M-current with IC50s of 0.75 µM, 0.71 µM, 0.6 μM, and 0.98 µM, respectively[3]. XE991 and DMP 543 may prove to be superior to linopirdine as Alzheimer's disease therapeutics. Although linopirdine possesses an EC50 of 4.2 microM for enhancement of [3H]ACh release from rat brain slices, XE991 and DMP 543 have EC50S of 490 and 700 nM, respectively. Although 5 mg/kg (p.o.) linopirdine does not lead to statistically significant increases in hippocampal extracellular acetylcholine levels, 5 mg/kg (p.o.) XE991 leads to increases (maximal effect > 90% over baseline) which are sustained for 60 min[4]. XE991 at 30 μM reduced the anti-contractile response of PVAT, but had no effects on vasocontraction induced by phenylephrine (PE) in the absence of PVAT (perivascular adipose tissue). 30 μM XE991 did not affect BKCa currents in VSMCs[5].
XE 991 2HCl 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Primary rat cortical neurons
300 nM
1 hour pretreatment, maintained for 24 hours
To evaluate the neuroprotective effect of XE-991 against GA toxicity, results showed XE-991 significantly improved cell viability and reduced mitochondrial ROS production.
Cell Death Discov. 2022 Sep 20;8(1):391
RA-differentiated SH-SY5Y cells
300 nM - 10 µM
1 hour pretreatment, maintained for 24 hours
To evaluate the neuroprotective effect of XE-991 against GA-induced cell damage, results showed XE-991 significantly improved cell survival and reduced mitochondrial ROS production.
Cell Death Discov. 2022 Sep 20;8(1):391
Primary rat microglia
30 µM
24 hours
XE-991 blockade of Kv7/KCNQ channels exclusively inhibited the migratory capacity of resting microglia without affecting survival, proliferation, phagocytic capacity, or activation state.
J Neuroinflammation. 2020 Apr 6;17(1):100
XE 991 2HCl 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Sprague-Dawley rats
Acute restraint stress model
Bilateral PVN microinjection
0.5 pmol in 100 nl of aCSF
Single injection
XE-991 significantly increased plasma corticosterone levels, and acute stress attenuated the excitatory effect of XE-991 on plasma corticosterone levels.
Neuropharmacology. 2017 Mar 1;114:67-76
Rats
Hemorrhagic shock model
Intravenous injection
1 mg/kg
Single dose
To evaluate the role of XE-991 in fluid resuscitation after hemorrhagic shock, results showed XE-991 significantly reduced the amount of fluid required for resuscitation
J Biomed Sci. 2017 Jan 17;24(1):8
Sprague Dawley rats
Rat mesenteric small arteries
In vitro incubation
10 μmol/L
Single dose, incubated for 30 minutes
To investigate the role of Kv7 channels in the PVAT anticontractile effect, results showed that XE 991 reversed the noradrenaline-induced anticontractile effect by inhibiting Kv7 channels in PVAT.
Br J Pharmacol. 2018 Sep;175(18):3685-3698
Rats
Spontaneously hypertensive rats (SHRs)
Microinjection into the central amygdala (CeA)
6.7 nmol
Single injection, effects lasted for 26.8±3.9 minutes
XE-991 increased arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) in WKY rats but had no significant effect in SHRs.
Cardiovasc Res. 2022 Jan 29;118(2):585-596
Borderline hypertensive rats (BHRs)
Chronic unpredictable stress (CUS) model
Bilateral microinjection into the CeA
6.7 nmol
Single injection
In unstressed BHRs, XE-991 increased sympathetic outflow and arterial blood pressure, but had no significant effect in CUS-treated BHRs.
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