Anti-Seizure Drugs in Development

Retigabine: It is a new anti-seizure molecule under development, has exhibited a broad spectrum of antiepileptic activity in animal models, which is believed to be due to its ability to enhance potassium currents mediated by human KCNQ2 and KCNQ3 potassium channels as well as augment GABA-medicated currents. The phase three trials of this drug Retigabine Efficacy and Safety Trial for Partial-Onset Epilepsy (RESTORE 1and 2) have demonstrated a linear dose effect in seizure reduction from 600 to 1200mg doses (22). Adverse events were most common at the 900 and 1200 mg doses, and tended to affect the central nervous system. At the 1200-mg dose, somnolence was the most common adverse event (22.6%), followed by dizziness (19.8%), confusion (17.9%), and speech disorder (16%). Treatment discontinuations were most common at the highest dose. Retigabine has the promise to open a new channel for seizure control by acting on potassium channel.

Lacosamide: It is another new antiepileptic drug in development. Recently it has been launched in UK as a new adjunctive therapy (dose 200-400mg/day) in the treatment of partial-onset seizures with or without secondary generalization in patients with seizure disorder aged 16 years and older. Its efficacy has been demonstrated in three randomized, double-blind, multicenter, placebo-controlled trials over 12 weeks maintenance period. Both the 200 mg/day dose and the 400 mg/day dose had a statistically significant median percentage seizure reduction compared with placebo (23). Lacosamide had no significant effect on laboratory values, body weight, or vital signs. The most common adverse events leading to withdrawal were diplopia and vomiting which were observed with higher (400 mg/day) dose.

Conclusion: In the present scenario, oxcarbazepine and topiramate are approved for initial monotherapy for partial seizures but lamotrigine, levetiracetam and gabapentin have also been found eligible to make to that grade. Others are also effective but at present they are at best the add-on drugs. While choosing an add-on drug, co-morbid conditions, safety and it's mechanism of action should be taken into consideration as well, for the best results. If the initial drug is working on sodium channel the second one should be working through GABA and vice versa.

References:

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Advance Access on 7th July 2009
Last updated on 1st September 2009. Vol 6 Issue 9 Art # 47

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Kumar CM. Second Generation Anti Seizure Drugs.Pediatric Oncall [serial online] 2009 [cited 2009 September 1];Vol 6 Art # 47. Available from: