From the Guidelines
Lamotrigine primarily works by blocking voltage-sensitive sodium channels in neurons, which inhibits the release of excitatory neurotransmitters, making it effective for both epilepsy and bipolar disorder. The mechanisms of action of lamotrigine are complex, but it is classified as a voltage-gated sodium channel (VGSC) modulator that inhibits VGSC, leading to inhibitory effects on excitatory neurotransmission 1. This action stabilizes neuronal membranes and prevents the excessive neuronal firing that contributes to seizures and mood instability. Additionally, lamotrigine may also affect sensory-perceptual functions, indicating the need to evaluate its effects on arousal and sensory-perceptual functions in pharmacological assessments 1.
Some key points about lamotrigine's mechanisms of action include:
- Inhibition of voltage-gated sodium channels, which reduces the release of excitatory neurotransmitters like glutamate and aspartate
- Potential effects on sensory-perceptual functions, which may impact its use in certain patients
- Classification as a VGSC modulator, which distinguishes it from other anticonvulsants like levetiracetam, a synaptic vesicle protein 2A (SV2A) modulator 1
- Lack of significant impact on GABA neurotransmission, unlike many other anticonvulsants
It's worth noting that while lamotrigine has a relatively long half-life and can be effective for both epilepsy and bipolar disorder, its use requires careful consideration of potential side effects and interactions with other medications 1. However, the most recent and highest quality study available 1 provides the most relevant information on lamotrigine's mechanisms of action, and its use as a VGSC modulator makes it a valuable option for patients with epilepsy and bipolar disorder.
From the Research
Mechanisms of Action of Lamotrigine
The mechanisms of action of lamotrigine involve several key processes:
- Stabilization of neuronal membranes through effects on voltage-sensitive sodium channels 2, 3, 4
- Inhibition of the release of excitatory neurotransmitters such as glutamate and aspartate 2, 5, 4
- Potential enhancement of GABAergic neurotransmission 6
- Modulation of the activity of voltage-gated ion channels, particularly those related to the inhibition of neuronal excitability 6
Effects on Neurotransmitter Release
Lamotrigine has been shown to:
- Inhibit the veratrine-evoked release of glutamate and aspartate, with ED50 values of 21 microM for both amino acids 4
- Be less potent in the inhibition of GABA release, with an ED50 value of 44 microM 4
- Have no effect on potassium-evoked amino acid release or on spontaneous release 4
Clinical Implications
The mechanisms of action of lamotrigine contribute to its efficacy in treating various neurological disorders, including: