Retigabine: in partial seizures.
Retigabine has anticonvulsant properties that appear to be primarily mediated by opening neuronal voltage-gated potassium channels. This action has been shown in neuronal KCNQ2/3 and KCNQ3/5 potassium channels. In addition to this unique action, retigabine also potentiates GABA-evoked currents in cortical neurons at high concentrations. When used as adjunctive therapy in patients with partial seizures, retigabine 600-1200 mg/day (200-400 mg three times daily) was associated with significant linear dose-dependent reductions in monthly seizure frequency compared with placebo in a large 16-week randomised phase II trial. Median monthly seizure frequency decreased from baseline by up to 35% among patients in the retigabine treatment arms compared with 13% in the placebo group. Retigabine 1200 mg/day was also significantly more effective than retigabine 600 mg/day. Responder rates, defined as the proportion of patients with > or = 50% reduction in seizure frequency, were significantly higher among patients in the retigabine 900 and 1200 mg/day groups than in those who received placebo. CNS-related adverse events were the most commonly reported treatment-emergent adverse events associated with retigabine in clinical trials. Across all three retigabine groups in the large phase II trial, somnolence (20.3%), dizziness (14.6%), confusion (12.3%) and speech disorder (11.3%) were the most frequent CNS-related adverse events.
Plosker
Greg L
GL
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Scott
Lesley J
LJ
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use*; D002219:Carbamates / Q000627:therapeutic use*; D004828:Epilepsies, Partial / Q000188:drug therapy*; D006801:Humans; D010655:Phenylenediamines / Q000627:therapeutic use*
D000927:Anticonvulsants; D002219:Carbamates; D010655:Phenylenediamines; C101866:ezogabine