Lamotrigine (marketed as Lamictal) is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. The precise mechanism(s) by which lamotrigine exerts its anticonvulsant action are unknown. In animal models designed to detect anticonvulsant activity, lamotrigine was effective in preventing seizure spread in the maximum electroshock (MES) and pentylenetetrazol (scMet) tests, and prevented seizures in the visually and electrically evoked after-discharge (EEAD) tests for antiepileptic activity. Lamotrigine also displayed inhibitory properties in the kindling model in rats both during kindling development and in the fully kindled state. The relevance of these models to human epilepsy, however, is not known. One proposed mechanism of action of lamotrigine, the relevance of which remains to be established in humans, involves an effect on sodium channels. In vitro pharmacological studies suggest that lamotrigine inhibits voltage-sensitive sodium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate). Effect of Lamotrigine on N-Methyl d-Aspartate-Receptor Mediated Activity Lamotrigine did not inhibit N-methyl d-aspartate (NMDA)-induced depolarizations in rat cortical slices or NMDA-induced cyclic GMP formation in immature rat cerebellum, nor did lamotrigine displace compounds that are either competitive or noncompetitive ligands at this glutamate receptor complex (CNQX, CGS, TCHP). The IC50 for lamotrigine effects on NMDA-induced currents (in the presence of 3 uM of glycine) in cultured hippocampal neurons exceeded 100 uM. The mechanisms by which lamotrigine exerts its therapeutic action in bipolar disorder have not been established. The mechanisms that underpin the passage of lamotrigine at the blood-brain barrier to its site of action in the brain is poorly understood.

Phenytoin is an anti-epileptic drug. Phenytoin has been used with much clinical success against all types of epileptiform seizures, except petit mal epilepsy. Phenytoin is a available for oral administration (tablets, capsules, suspension). CEREBYX® (fosphenytoin sodium injection) is a prodrug intended for parenteral administration; its active metabolite is phenytoin. CEREBYX should be used only when oral phenytoin administration is not possible. Although several potential targets for phenytoin action have been identified within the CNS (Na-K-ATPase, the GABAA receptor complex, ionotropic glutamate receptors, calcium channels and sigma binding sites) to date, though, the best evidence hinges on the inhibition of voltage-sensitive Na channels in the plasma membrane of neurons undergoing seizure activity.

Oxcarbazepine and its active metabolite (10,11-dihydro-10-hydroxy-carbazepine, MHD) have been effective in animal models of epilepsy that generally predict efficacy in generalized tonic-clonic seizures and partial seizures in humans. The pharmacokinetic profile of oxcarbazepine is less complicated than that of carbamazepine, with less metabolism by the cytochrome P450 system, no production of an epoxide metabolite, and lower plasma protein binding. The clinical efficacy and tolerability of oxcarbazepine have been demonstrated in trials in adults, children, and the elderly. The pharmacological activity of oxcarbazepine is primarily exerted through the 10-monohydroxy metabolite (MHD) of oxcarbazepine. The precise mechanism by which oxcarbazepine and MHD exert their antiseizure effect is unknown; however, in vitro electrophysiological studies indicate that they produce blockade of voltage-sensitive sodium channels, resulting in stabilization of hyperexcited neural membranes, inhibition of repetitive neuronal firing, and diminution of propagation of synaptic impulses. These actions are thought to be important in the prevention of seizure spread in the intact brain. In addition, increased potassium conductance and modulation of high-voltage activated calcium channels may contribute to the anticonvulsant effects of the drug.

Carbamazepine is an analgesic, anti-epileptic agent that is FDA approved for the treatment of epilepsy, trigeminal neuralgia. It appears to act by reducing polysynaptic responses and blocking the post-tetanic potentiation. It depresses thalamic potential and bulbar and polysynaptic reflexes, including the linguomandibular reflex in cats. Commonly reported side effects of carbamazepine include: dizziness, drowsiness, nausea, ataxia, and vomiting. Carbamazepine is a potent inducer of hepatic CYP1A2, 2B6, 2C9/19, and 3A4 and may reduce plasma concentrations of concomitant medications mainly metabolized by CYP1A2, 2B6, 2C9/19, and 3A4 through induction of their metabolism, like Boceprevir, Cyclophosphamide, Aripiprazole, Tacrolimus, Temsirolimus and others.

Phenytoin is an anti-epileptic drug. Phenytoin has been used with much clinical success against all types of epileptiform seizures, except petit mal epilepsy. Phenytoin is a available for oral administration (tablets, capsules, suspension). CEREBYX® (fosphenytoin sodium injection) is a prodrug intended for parenteral administration; its active metabolite is phenytoin. CEREBYX should be used only when oral phenytoin administration is not possible. Although several potential targets for phenytoin action have been identified within the CNS (Na-K-ATPase, the GABAA receptor complex, ionotropic glutamate receptors, calcium channels and sigma binding sites) to date, though, the best evidence hinges on the inhibition of voltage-sensitive Na channels in the plasma membrane of neurons undergoing seizure activity.