Neuronal potassium channel openers in the management of epilepsy: role and potential of retigabine
Vincenzo Barrese1, Francesco Miceli2, Maria Virginia Soldovieri3, Paolo Ambrosino3, Fabio Arturo Iannotti3, Maria Roberta Cilio2, Maurizio Taglialatela1,3
1Department of Neuroscience, University of Naples Federico II, Naples; 2Division of Neurology, IRCCS Bambino Gesù Children's Hospital, Rome; 3Department of Health Science, University of Molise, Campobasso, Italy
Abstract: 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.
Keywords: epilepsy, retigabine, potassium channels, antiepileptic drugs, Kv7 channels
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