lamotrigine brands

Molecular formula: C9H7Cl2N5

The exact mechanism of action of lamotrigine is not fully elucidated, as it may exert cellular activities that contribute to its efficacy in a range of conditions. Although chemically unrelated, lamotrigine actions resemble those of phenytoin and carbamazepine, inhibiting voltage-sensitive sodium channels, stabilizing neuronal membranes, thereby modulating the release of presynaptic excitatory neurotransmitters. Lamotrigine likely acts by inhibiting sodium currents by selective binding to the inactive sodium channel, suppressing the release of the excitatory amino acid, glutamate. The mechanism of action of lamotrigine in reducing anticonvulsant activity is likely the same in managing bipolar disorder. Studies on lamotrigine have identified its binding to sodium channels in a fashion similar to local anesthetics, which could explain the demonstrated clinical benefit of lamotrigine in some neuropathic pain states. Lamotrigine displays binding properties to several different receptors. In laboratory binding assays, it demonstrates weak inhibitory effect on the serotonin 5-HT3 receptor. Lamotrigine also weakly binds to Adenosine A1/A2 receptors, α1/α2/β adrenergic receptors, dopamine D1/D2 receptors, GABA A/B receptors, histamine H1 receptors, κ-opioid receptor (KOR), mACh receptors and serotonin 5-HT2 receptors with an IC50>100 µM. Weak inhibitory effects were observed at sigma opioid receptors. An in vivo study revealed evidence that lamotrigine inhibits Cav2.3 (R-type) calcium currents, which may also contribute to its anticonvulsant effects. Spectrophotometry with the Ca(++)-sensitive dye fura-2 was used to study the effect of lamotrigine (LAG) on the depolarization-evoked Ca++ influx in the acutely isolated basolateral amygdala neurons. Depolarization of the neurons with high K+ resulted in the elevation of intracellular Ca++ concentration [Ca++]i in a concentration-dependent manner. The K(+)-induced Ca++ influx was completely blocked in the Ca(++)-free solution or by Cd++, indicating that depolarization-induced increases in [Ca++]i were triggered largely, if not completely, by Ca++ entry from extracellular space and Ca++ entry occurred through voltage-dependent Ca++ channels. Application of LAG reduced the depolarization-evoked Ca++ influx in a concentration-dependent manner. The effect of LAG was markedly reduced in the presence of N-type Ca++ channel blocker omega-conotoxin-GVIA (omega-CgTX). These results suggest that the action of LAG is mediated, at least in part, by the modulation of N-type Ca++ channels. Lamotrigine (LAG) is an antiepileptic drug which is believed to suppress seizures by inhibiting the release of excitatory neurotransmitters. The present study was aimed at investigating the effect of LAG on the 4-aminopyridine (4AP)-evoked glutamate release in cerebrocortical nerve terminals (synaptosomes). LAG inhibited the release of glutamate evoked by 4AP in a concentration-dependent manner. This inhibitory effect was associated with a reduction in the depolarization-evoked increase in the cytoplasmic free Ca2+ concentration ([Ca2+]C). In addition, LAG did not alter the resting synaptosomal membrane potential or 4AP-evoked depolarization. Furthermore, ionomycin-evoked glutamate release was not affected by LAG. Based on these results, we suggest that presynaptic calcium influx blockade and inhibition of glutamate release may underlie the mechanism of action of LAG. These action may also contribute to their neuroprotective properties in excitotoxic injury.

Source: PubChem (NCBI) · compound 3878