ICA-27243 is a selective, potent and orally active KCNQ2/Q3 potassium channel opener with an EC50 value of 0.38 μM. ICA-27243 is less effective in activating KCNQ4 and KCNQ3/Q5. ICA-27243 exhibits antiepileptic and anticonvulsant effects[1][2]. In SH-SY5Y human neuroblastoma cells, ICA-27243 produces membrane potential hyperpolarisation, which is prevented in combination with the M-current inhibitors XE-991 and Linopirdine. In CHO cells stably expressing heterotrimeric KCNQ2/Q3 channels, ICA-27243 enhanced 86Rb+ efflux (EC50=0.2 μM) and whole-cell currents (EC50=0.4 μM). Activation of KCNQ2/Q3 channels was associated with a voltage-dependent hyperpolarising shift in channel activation (V1/2 shifted to -19 mV at 10 μM)[1].
ICA-27243 细胞实验
Cell Line
Concentration
Treated Time
Description
References
dorsal root ganglion neurons
10 µM
8 days
To evaluate the effect of ICA-27243 on axonal growth of dorsal root ganglion neurons, results showed that ICA-27243 tended to decrease axonal elongation.
Int J Mol Sci. 2024 Jul 3;25(13):7327
dorsal root ganglion neurons
10 µM
4 days
To evaluate the effect of ICA-27243 on axonal growth of dorsal root ganglion neurons, results showed that ICA-27243 tended to decrease axonal elongation.
Int J Mol Sci. 2024 Jul 3;25(13):7327
F11 cells
3 μM
7–8 min
ICA-27243 inhibited CAP-induced [Ca2+]i increases, with effects similar to RTG
Int J Mol Sci. 2019 Sep 4;20(18):4322
F11 cells
1–20 μM
7–8 min
ICA-27243 dose-dependently inhibited BK-induced [Ca2+]i increases, with a maximal inhibition of ~60% and an IC50 of ~5 μM
Int J Mol Sci. 2019 Sep 4;20(18):4322
Cryopreserved dorsal root ganglion neurons
10 μM
10 seconds
To test the hyperpolarization effect of ICA-27243 on cryopreserved dorsal root ganglion neurons, results showed cryopreservation did not affect the hyperpolarization effect of ICA-27243.
Mol Pain. 2018 Jan-Dec;14:1744806917749669
Dorsal root ganglion neurons (Wistar rats)
10 μM
10 seconds
To test the hyperpolarization effect of ICA-27243 on dorsal root ganglion neurons from Wistar rats, results showed a weaker hyperpolarization effect of ICA-27243.
Mol Pain. 2018 Jan-Dec;14:1744806917749669
Dorsal root ganglion neurons (SD rats)
10 μM
10 seconds
To test the hyperpolarization effect of ICA-27243 on dorsal root ganglion neurons from SD rats, results showed ICA-27243 significantly hyperpolarized the neuronal membrane potential.
Mol Pain. 2018 Jan-Dec;14:1744806917749669
spinal cord organotypic cultures (SCOCs)
10 μM
30 min
prevented MN degeneration under acute excitotoxic conditions
Neurotherapeutics. 2024 Mar;21(2):e00319
ICA-27243 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Transgenic SOD1G93A mice
ALS transgenic mouse model
Intraperitoneal injection
10 mg/kg/day
Daily administration until the end of the experiment
Improved neuromuscular function, maintained motor coordination, reduced spinal motor neuron death and glial reactivity
Neurotherapeutics. 2024 Mar;21(2):e00319
Rats
Spontaneously hypertensive rats (SHR) and normotensive rats (WKY)
Intravenous injection
11.2 µmol/kg
Single dose, observed for 15 minutes
ICA-27243 increased tyramine-stimulated norepinephrine overflow and epinephrine secretion in female SHR and reduced the TPR-response to tyramine in female SHR.
Front Physiol. 2018 Feb 20;9:117
ICA-27243 动物研究
Animal study
Administered orally at doses of 1-100 mg/kg, ICA-27243 exhibits anticonvulsant activity in a mouse model of maximal electroshock epilepsy with an ED50 value of 8.4 mg/kg[1].
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