Table 2 Mechanism of action of the 8 newly approved antiepileptic drugs (AEDs) <table><thead><tr><th>AED</th><th>Mechanism of action</th></tr></thead><tbody><tr><td>Clobazam</td><td>Binding to benzodiazepine at the GABA_A ligand-gated chloride channel complex</td></tr><tr><td>Eslicarbazepine</td><td>Use-dependent blockage of voltage-sensitive sodium channels</td></tr><tr><td>Ezogabine</td><td>Positive allosteric modulator of KCNQ2-5; positive allosteric modulator of GABA_A receptors</td></tr><tr><td>Lacosamide</td><td>Slow inactivation of voltage-gated sodium channels; binds to CRMP-2</td></tr><tr><td>Perampanel</td><td>AMPA receptor antagonist</td></tr><tr><td>Pregabalin</td><td>Binding to the α2-δ protein subunit of voltage-gated calcium channels</td></tr><tr><td>Rufinamide</td><td>Use-dependent blockage of voltage-sensitive sodium channels</td></tr><tr><td>Vigabatrin</td><td>Inactivation of GABA transaminase</td></tr></tbody></table>

This pathophysiology diagram illustrates the four-stage mechanism of a voltage-gated sodium (Na+) ion channel embedded in a lipid bilayer, focusing on the mechanical and electrostatic changes during depolarization. (1) Resting: The channel's coiled helices are closed, maintaining an electrostatic insulating seal across the 10 nm membrane. (2) Moment of Threshold: An approaching membrane soliton (mechanical wave) exerts pressure, displacing helices and disrupting the electrical insulation. This allows Na+ ions to enter the pore and interact with hydrophilic, negatively charged interior surfaces. (3) Threshold Forces: Inward Na+ influx creates electrostatic attraction (red arrows) toward the intracellular space. Mechanical 'iris-like' opening and contraction occur, causing lateral membrane expansion (green arrows) and a net intracellular force vector (blue arrow). (4) Refractory: Positive charge equalization occurs on the intracellular side, leading to pore closure. The channel remains in a refractory state with localized Na+ accumulation until charges are cleared by diffusion, preventing immediate reactivation.

A medical schematic diagram illustrating the direct nose-to-brain delivery of phenytoin sodium loaded Nanostructured Lipid Carriers (NLCs) via the olfactory epithelial pathway. The illustration is divided into a sagittal anatomical view of the human head and a detailed inset of the cellular transport mechanism. The primary anatomical view shows the route of intranasal administration with NLCs depositing on the olfactory mucosa. The inset highlights the extracellular transport mechanism through the olfactory epithelium. It depicts NLCs of different sizes (<50nm and >100nm) moving through open intercellular clefts in the olfactory mucosa, traversing the lamina propria, and crossing the cribriform plate. The diagram shows the particles being transported through the perineural space and along olfactory ensheathing cells to reach the olfactory bulb and eventually the brain. Annotations specify that the smaller <50nm phenytoin sodium NLCs reach the brain faster than larger particles. This educational visual explains the pathophysiology and pharmacology of bypass-blood-brain-barrier drug delivery systems for acute seizure management.