Lacosamide is a newer antiepileptic that differs from carbamazepine despite both acting on sodium channels. Which property is unique to lacosamide?

• A Selectively enhances slow inactivation of voltage-gated sodium channels without affecting fast inactivation ✓
• B Stabilizes fast inactivated state of sodium channels like carbamazepine but with higher receptor affinity
• C Blocks the persistent sodium current through Nav1.1 channels selectively in GABAergic interneurons
• D Binds to the alpha-2-delta subunit of voltage-gated calcium channels, reducing sodium channel trafficking

Explanation

Lacosamide selectively enhances the slow inactivation of voltage-gated sodium channels (predominantly Nav1.7 and Nav1.3). This is mechanistically distinct from traditional sodium channel blockers like carbamazepine, phenytoin, and lamotrigine, which primarily stabilize the fast inactivated state of the channel. Slow inactivation is a prolonged, more stable form of channel inactivation that develops during sustained depolarizations characteristic of high-frequency epileptic firing. By enhancing this state, lacosamide selectively dampens pathological repetitive firing without affecting physiological fast inactivation needed for normal neuronal signalling. Lacosamide also binds to CRMP-2 (collapsing response mediator protein-2), though this mechanism's clinical relevance is less established.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.