Mechanism of action<unk>  is a member of the sodium channel blocking class of antiepileptic drugs. This may suppress the release of glutamate and aspartate, two dominant excitatory neurotransmitters in the central nervous system. It is generally accepted to be a member of the sodium channel blocking class of antiepileptic drugs, but it could have additional actions, since it has a broader spectrum of action than other sodium channel antiepileptic drugs such as phenytoin and is effective in the treatment of the depressed phase of bipolar disorder, whereas other sodium channel-blocking antiepileptic drugs are not, possibly on account of its sigma receptor activity. In addition,<unk>  shares few side effects with other, unrelated anticonvulsants known to inhibit sodium channels, which further emphasizes its unique properties. It is a triazine derivate that inhibits voltage-sensitive sodium channels, leading to stabilization of neuronal membranes. It also blocks L-, N-, and P-type calcium channels and weakly inhibits the serotonin 5-HT3 receptor. These actions are thought to inhibit release of glutamate at cortical projections in the ventral striatum limbic areas, and its neuroprotective and antiglutamatergic effects have been pointed out as promising contributors to its mood stabilizing activity. Observations that<unk>  reduced γ-aminobutyric acid (GABA) A receptor-mediated neurotransmission in rat amygdala, suggest that a GABAergic mechanism may also be involved. It appears that<unk>  does not increase GABA blood levels in humans.<unk>  does not have pronounced effects on any of the usual neurotransmitter receptors that anticonvulsants affect (adrenergic, dopamine D1 and D2, muscarinic, GABA, histaminergic H1, serotonin 5-HT2, and N-methyl-D-aspartate). Inhibitory effects on 5-HT, norepinephrine, and dopamine transporters are weak.<unk>  is a weak inhibitor of dihydrofolate reductase, but whether this effect is sufficient to contribute to a mechanism of action or increases risk to the fetus during pregnancy is not known. Early studies of<unk> 's mechanism of action examined its effects on the release of endogenous amino acids from rat cerebral cortex slices in vitro. As is the case for antiepileptic drugs that act on voltage-dependent sodium channels,<unk>  thereby inhibits the release of glutamate and aspartate, which is evoked by the sodium-channel activator veratrine, and was less effective in the inhibition of acetylcholine or GABA release. At high concentrations, it had no effect on spontaneous or potassium-evoked amino acid release. These studies suggested that<unk>  acts presynaptically on voltage-gated sodium channels to decrease glutamate release. Several electrophysiological studies have investigated the effects of<unk>  on voltage-gated sodium channels. For example,<unk>  blocked sustained repetitive firing in cultured mouse spinal cord neurons in a concentration-dependent manner, at concentrations that are therapeutically relevant in the treatment of human seizures. In cultured hippocampal neurons,<unk>  reduced sodium currents in a voltage-dependent manner, and at depolarised potentials showed a small frequency-dependent inhibition. These and a variety of other results indicate that the antiepileptic effect of<unk> , like those of phenytoin and carbamazepine, is at least in part due to use- and voltage-dependent modulation of fast voltage-dependent sodium currents. However,<unk>  has a broader clinical spectrum of activity than phenytoin and carbamazepine and is recognised to be protective against generalised absence epilepsy and other generalised epilepsy syndromes, including primary generalised tonic–clonic seizures, juvenile myoclonic epilepsy, and Lennox-Gastaut syndrome. The basis for this broader spectrum of activity of<unk>  is unknown, but could relate to actions of the drug on voltage-gated calcium channels.<unk>  blocks T-type calcium channels weakly, if at all. However, it does inhibit native and recombinant high voltage–gated calcium channels (N- and P/Q/R-types) at therapeutic concentrations. Whether this activity on calcium channels accounts for<unk> 's broader clinical spectrum of activity in comparison with phenytoin and carbamazepine remains to be determined. It antagonises these receptors with the following IC50 values: * 5-HT3, IC50 = 18μM * σ receptors, IC50 = 145μM Pharmacokinetics The pharmacokinetics of<unk>  follow first-order kinetics, with a half-life of 29 hours and volume of distribution of 1.36L/kg.<unk>  is rapidly and completely absorbed after oral administration. Its absolute bioavailability is 98% and its plasma Cmax occurs from 1.4 to 4.8 hours. Available data indicate that its bioavailability is not affected by food. Estimate of the mean apparent volume of distribution of<unk>  following oral administration ranges from 0.9 to 1.3L/kg. This is independent of dose and is similar following single and multiple doses in both patients with epilepsy and in healthy volunteers.<unk>  is inactivated by glucuronidation in the liver.<unk>  is metabolized predominantly by glucuronic acid conjugation. Its major metabolite is an inactive 2-n-glucuronide conjugate.<unk>  has fewer drug interactions than many anticonvulsant drugs, although pharmacokinetic interactions with carbamazepine, phenytoin and other hepatic enzyme inducing medications may shorten half-life. Dose adjustments should be made on clinical response, but monitoring may be of benefit in assessing compliance. The capacity of available tests to detect potentially adverse consequences of melanin binding is unknown. Clinical trials excluded subtle effects and optimal duration of treatment. There are no specific recommendations for periodic ophthalmological monitoring.<unk>  binds to the eye and melanin-containing tissues which can accumulate over time and may cause toxicity. Prescribers should be aware of the possibility of long-term ophthalmologic effects and base treatment on clinical response. Patient compliance should be periodically reassessed with lab and medical testing of liver and kidney function to monitor progress or side effects.
Lamotrigine
Mesuximide
Propazepine
Topiramate
Ethosuximide
Tiagabine
Carbamazepine
Levetiracetam