Mechanism of Action of Lamotrigine
Lamotrigine functions primarily as a voltage-gated sodium channel (VGSC) modulator that inhibits these channels, thereby stabilizing presynaptic neuronal membranes and preventing the excessive release of excitatory neurotransmitters, particularly glutamate and aspartate. 1
Primary Mechanism
- Lamotrigine blocks voltage-dependent sodium channels, which represents its fundamental mechanism of action 2
- This blockade stabilizes the presynaptic neuronal membrane, preventing abnormal neuronal firing 3
- The stabilization effect inhibits the release of excitatory neurotransmitters glutamate and aspartate into the postsynaptic neuron 3, 4
- This inhibitory effect on excitatory neurotransmission is the basis for both its antiepileptic and mood-stabilizing properties 1
Clinical Implications of the Mechanism
- As a VGSC modulator, lamotrigine has less impact on arousal function compared to benzodiazepines, though it may still affect sensory-perceptual functions 1
- The antiglutamatergic properties may explain its antidepressant and mood-stabilizing effects in bipolar disorder 5
- Studies demonstrate that veratrine (a sodium channel opener) reverses lamotrigine's antidepressant-like effects, confirming that sodium channel blockade is essential to its therapeutic action 6
- This mechanism differs from traditional antidepressants (TCAs and SSRIs), whose effects are not reversed by sodium channel openers 6
Functional Domain Effects
- Pharmacodynamic studies show lamotrigine at doses of 50-300 mg/day demonstrates no statistically significant impairment in arousal function, sensory-perceptual functions, or cognitive functions 1
- This favorable profile distinguishes it from other VGSC modulators like carbamazepine, which shows significant impairment in these domains 1