Lacosamide's antiepileptic mechanism involves 'slow inactivation' of sodium channels rather than the 'fast inactivation' promoted by carbamazepine. Which molecular feature of lacosamide facilitates this slow-inactivation selectivity?

• A Binding to the collapsin response mediator protein-2 (CRMP-2), modulating slow inactivation ✓
• B Binding to the local anaesthetic binding site within the channel pore during rapid firing
• C Allosteric modulation of beta-subunit of the sodium channel complex
• D Phosphorylation of Ser1966 on the Nav1.1 alpha-subunit to enhance slow inactivation

Explanation

Lacosamide has a dual mechanism: it enhances the slow inactivation state of voltage-gated sodium channels (reducing sustained repetitive firing without blocking fast transient channel activity), and it binds to CRMP-2 (collapsin response mediator protein-2), a protein involved in neuronal signal transduction. The interaction with CRMP-2 is unique to lacosamide among AEDs and is thought to contribute to its slow-inactivation selectivity. Traditional sodium-channel AEDs like carbamazepine/phenytoin stabilise fast inactivation by binding to the open-channel pore (local anaesthetic binding site). Beta-subunit modulation and direct phosphorylation are not lacosamide's mechanism.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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