Cell lines

Chinese hamster ovary (CHO-K1) cells transfected with the KCNQ2/Q3 tandem construct (CHO-KCNQ2/Q3)

Preparation method

This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

0.1 ~ 10 μM

Applications

Retigabine Dihydrochloride (0.1 ~ 10 μM) induced a potassium current and hyperpolarized CHO-KCNQ2/Q3 cells but not in wild-type cells.

Animal models

Mouse 6-Hz psychomotor seizure models

Dosage form

26 or 33 mg/kg; i.p.

Applications

In the 6-Hz psychomotor seizure model, Retigabine Dihydrochloride dose-dependently blocked seizures induced by either 32 or 44 mA current stimulation.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

IC50: N/A

Retigabine is a first-in-class K+ channel (KCNQ) opener. KCNQ channels are reported to be expressed predominantly in neurons and are critical determinants of cellular excitability, as shown by the occurrence of human genetic mutations in KCNQ channels which underlie inheritable disorders including the syndrome of benign familial neonatal convulsions.

In vitro: Retigabine was found to combine a novel mode of actions, which were namely potassium channel opening (KCNQ2, KCNQ3 as well as KCNQ4 channels). Retigabine also showed activities with some potentiation of gamma amino butyric acid (GABA)-evoked currents at its higher concentrations [1].

In vivo: Animal models of epileptic seizures showed that retigabine treatment was effective at an oral dose as low as 0.01 mg/kg. Studies performed in mice also indicated that combining retigabine with another anticonvulsant agent leads to an additive effect [1].

Clinical trial: A clinical interaction study showed that there was no pharmacokinetic interaction between phenobarbitone and retigabine in healthy subjects. Thus, no dosage adjustment is likely to be necessary when phenobarbitone and retigabine are coadministered to patients [1].

Reference:
[1] Ferron GM,Patat A,Parks V,Rolan P,Troy SM.  Lack of pharmacokinetic interaction between retigabine and phenobarbitone at steady-state in healthy subjects. Br J Clin Pharmacol.2003 Jul;56(1):39-45.