Retigabine (Trobalt, Potiga) — General Discussion

8-9/10 to 0-2/10.

Tapered up to 300 mg TID.

 

I think he only tried it for a day.

 

In light of recent discussions about the share of GABA modulation in the tinnitus/hyperacusis alleviation of Retigabine:



Considering in vitro pharmacological data in the context of the mean free Cmax and Cave achieved with Retigabine in humans highlights the striking overlap between the efficacious concentrations of the drug and its most potent activity at KCNQ channels such as KCNQ2/3. Indeed, concentrations some 10-fold higher than achieved at the maximum dose of 1,200 mg/day used in patients with epilepsy could be required for significant effects on other receptor systems.

Modulation of GABAergic neurotransmission is an MoA relevant to the efficacy of several other AEDs; however, in in-vivo efficacy studies of Retigabine conducted in the mouse MES model or a rapid kindling model of epilepsy in the rat, co-administration of the KCNQ antagonist XE-991 reversed the anticonvulsant effects of Retigabine/Ezogabine, suggesting a lack of contribution by additional mechanisms. Overall, these data combined with the clinical setting assessments clearly support the conclusion that the primary MoA of Retigabine/Ezogabine involves activity at KCNQ channels such as KCNQ2/3.

The potentiating effects [of Retigabine on GABAa] were not inhibited by the benzodiazepine site antagonist flumazenil, indicating that the action of Retigabine/Ezogabine is not through the benzodiazepine site on the receptor.

Questions:

• What about the GABAb and GABAc receptors?
• Study still relevant?