Retigabine/Ezogabine, a KCNQ/K(V)7 channel opener: pharmacological and clinical data.
BACKGROUND
Epilepsy is a serious and common chronic neurological disease with an urgent need for novel treatment options, because 30% of all epilepsy patients do not respond to currently available drugs. Retigabine/Ezogabine (RTG) is a third-generation antiepileptic drug (AED) with a novel mechanism of action. It enhances the activity of voltage-gated K(V)7 potassium channels.


METHODS
The mechanism of action of RTG is reported in this paper, along with its pharmacodynamics and pharmacokinetics, based on a literature search from 1995 to 2011. Assessment of clinical efficacy and safety was performed using the published data of one Phase II and two Phase III clinical trials (RESTORE 1 and 2).


CONCLUSIONS
RTG is an efficacious AED with a unique mechanism of action. It offers a new treatment option which could be particularly interesting for patients who are resistant to currently available AEDs. However, future investigations will show if such a "rational drug therapy" will be truly advantageous. RTG seems to have a low interaction profile, but its interactions with lamotrigine in particular should be further explored. Side effects are common and mainly related to the central nervous system, but also affect peripheral organs, such as the bladder, due its relaxing effect on smooth muscle. Slow titration could be an option to reduce such side effects.
Abteilung Neurologie Mit Schwerpunkt Epileptologie, Hertie-Institut für Klinische Hirnforschung, Universität Tübingen, Tübingen, Germany.
Gökce
G
Orhan
Thomas V
TV
Wuttke
Anne T
AT
Nies
Matthias
M
Schwab
Holger
H
Lerche
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D002219:Carbamates / Q000494:pharmacology / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D051656:KCNQ Potassium Channels / Q000502:physiology; D049990:Membrane Transport Modulators / Q000494:pharmacology / Q000627:therapeutic use; D010655:Phenylenediamines / Q000494:pharmacology / Q000627:therapeutic use*
D000927:Anticonvulsants; D002219:Carbamates; D051656:KCNQ Potassium Channels; D049990:Membrane Transport Modulators; D010655:Phenylenediamines; C101866:ezogabine