Antiepileptic — retigabine
Epilepsy is a brain disorder, where electrical misfiring leads to sudden seizures. Normal human functions such as thoughts and emotions are the result of electrical excitation in the brain that takes place in an orderly fashion. When an epileptic patient has a seizure, these electrical signals become highly disorganised.
A number of antiepileptic drugs are available which reduce the incidence of seizures, including sodium valproate, which is thought to inhibit the action of GABA in the brain.
A new anticonvulsant under investigation is retigabine, formerly known as D-23129. The compound has been found to be an effective anticonvulsant in a range of in vitro and in vivo models. It has been shown in animal models to have a comparable activity spectrum to valproate, but it is effective at lower doses, and has a better side-effect profile.1
The drug has been shown to be a potent K+ channel opener in neuronal cells, and it is thought that the interaction may be selective for a currently unknown channel. In addition to this, retigabine increases the release of newly-synthesised GABA.
The compound has also been shown to have an additive effect when administered in combination with classical anticonvulsants, notably diazepam, phenobarbital, phenytoin and valproate, in animal studies.
Succesful Phase I trials with single and multiple doses showed its tolerability and favourable pharmakinetic behaviour. The compound is currently undergoing Phase II clinical trials to evaluate its effectiveness as an anticonvulsant.