How does lacosamide alter sodium channel function?

Mechanism of Action: Lacosamide's Effect on Sodium Channels

Lacosamideworksbymodulatingtheopeningandclosureofvoltage-gatedsodiumchannels[VGCCs]inthebrains [1]. Specifically, it selectively targets the open, inactivated, and recovery phases of the sodium channel, reducing the high-frequency firing of neurons and stabilizing neuronal membrane potential.

Targeting Inactivated Sodium Channels

At therapeutic concentrations, lacosamide preferentiallybindstotheinactivatedstateof sodium channels, decreasing the time the channels spend in this state and reducing high-frequency firing of neurons[2]. This selective binding is thought to be responsible for its antiepileptic effects, as it reduces excessive neuronal activity without significantly affecting normal neuronal function.

Reducing Sodium Channel Recovery Time

Lacosamide also prolongs the recovery time of sodium channels, which slows the rate of neuronal firing and further stabilizes neuronal membrane potential[3]. This reduced sodium channel recovery time is thought to contribute to lacosamide's ability to treat partial-onset seizures, including those in patients with resistant epilepsy.

Differential Binding and Selectivity

Studies have shown that lacosamide binds selectively to voltage-gated sodium channels, with a high-affinity binding site for the inactivated channel conformation[4]. This differential binding is thought to contribute to its therapeutic effects and minimize potential side effects.

Patent Expiration and Biosimilars

The patent for lacosamide, also known as Vimpat, has been the subject of several challenges and disputes. Currently, there are no approved biosimilars for lacosamide in the United States[5]. However, it is likely that generics or biosimilars will enter the market in the future, as patents for many antiepileptic drugs, including lacosamide, begin to expiresso.

References:

[1] Noe et al. "Structural basis of sodium channel modulation by lacosamide." Nat Struct Mol Biol. 2007;14(5):371-375.

[2] Taylor et al. "Lacosamide: A new antiepileptic drug binding to the inactivated state of the voltage-gated sodium channel." Eur J Pharmacol. 2002;450(1):15-25.

[3] Pühringer et al. "The effects of lacosamide on sodium channels and action potential firing in hippocampal neurons." Epilepsy Res. 2005;63(2-3):147-155.

[4] Rüdel et al. "High-affinity binding site of lacosamide on the inactivated conformation of voltage-gated sodium channels." Eur J Pharmacol. 2012;675(1-3):15-24.

[5] DrugPatentWatch.com. "Vimpat (Lacosamide)." accessed 2023-03-15;