Despite the availability of over 20
antiepileptic drugs, about 30% of epileptic patients do not achieve seizure control. Thus, identification of additional molecules targeting novel molecular mechanisms is a primary effort in today's
antiepileptic drug research. This paper reviews the pharmacological development of
retigabine, an
antiepileptic drug with a novel mechanism of action, namely the activation of
voltage-gated potassium channels of the Kv7 subfamily. These channels, which act as widespread regulators of intrinsic neuronal excitability and of
neurotransmitter-induced network excitability changes, are currently viewed among the most promising targets for
anticonvulsant pharmacotherapy. In particular, the present work reviews the pathophysiological role of Kv7 channels in neuronal function, the molecular mechanisms involved in the Kv7 channel-opening action of
retigabine, the activity of
retigabine in preclinical in vitro and in vivo studies predictive of
anticonvulsant activities, and the clinical status of development for this
drug as an add-on treatment for pharmacoresistant
epilepsy. Particular efforts are devoted to highlighting the potential advantages and disadvantages of
retigabine when compared with currently available compounds, in order to provide a comprehensive assessment of its role in
therapy for treatment-resistant
epilepsies.