Antiepileptic drugs of the phenyltriazine class.
Pharmacology
Antiepileptic drugs of the phenyltriazine class.
Mechanism of action
The exact mechanism of the anticonvulsant action of lamotrigine is unknown. In animal models designed to measure anticonvulsant activity, lamotrigine has been shown to be effective in preventing seizures in the maximal shock and pentylenetetrazole tests, and to prevent seizures in tests in which seizures are triggered by visual stimuli or electrical current. Lamotrigine also exhibited inhibitory properties in the rat kindling model both during stimulation and in the steady state kindling. However, the applicability of these models to human epilepsy is unknown.
One of the proposed mechanisms of action of lamotrigine, the significance of which in humans has yet to be established, is related to the effect on sodium channels. Pharmacological studies in vitro show that lamotrigine inhibits voltage-gated sodium channels, thereby stabilizing neuronal membranes and therefore modulating the release of presynaptic excitatory amino acid mediators (eg, glutamate and aspartate).
Effect of lamotrigine on N-methyl-D-aspartate receptor-mediated activity
Lamotrigine did not inhibit N-methyl-D-aspartate (NMDA)-induced depolarization in rat cortical sections or NMDA-induced cGMP production in immature rat cerebellum, nor did it displace compounds that are competitive or non-competitive glutamate receptor ligands (CNQX). , CGS, TCHP). The IC50 of lamotrigine for NMDA-induced ion currents (in the presence of 3 μmol glycine) in cultured hippocampal neurons exceeded 100 μmol.
The mechanism of therapeutic action of lamotrigine in bipolar disorder has not been established.
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