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.

Felbamate is an antiepileptic indicated as monotherapy or as an adjunct to other anticonvulsants for the treatment of partial seizures resulting from epilepsy. Receptor-binding studies in vitro indicate that felbamate has weak inhibitory effects on GABA-receptor binding, benzodiazepine receptor binding, and is devoid of activity at the MK-801 receptor binding site of the NMDA receptor-ionophore complex. However, felbamate does interact as an antagonist at the strychnine-insensitive glycine recognition site of the NMDA receptor-ionophore complex. The mechanism by which felbamate exerts its anticonvulsant activity is unknown, but in animal test systems designed to detect anticonvulsant activity, felbamate has properties in common with other marketed anticonvulsants. In vitro receptor binding studies suggest that felbamate may be an antagonist at the strychnine-insensitive glycine-recognition site of the N-methyl-D-aspartate (NMDA) receptor-ionophore complex. Antagonism of the NMDA receptor glycine binding site may block the effects of the excitatory amino acids and suppress seizure activity. Animal studies indicate that felbamate may increase the seizure threshold and may decrease seizure spread. It is also indicated that felbamate has weak inhibitory effects on GABA-receptor binding, benzodiazepine receptor binding. Felbamate should be used only in those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia and/or liver failure is deemed acceptable in light of the benefits conferred by its use. Felbatol is the brand name used in the United States for felbamate.

Gabapentin enacarbil (Horizant in USA, Regnite in Japan), is a prodrug of gabapentin, an antiepileptic drug (AED). It was designed for increased oral bioavailability over gabapentin and to be transported through two high capacity transporters in the intestine, sodium-dependent multivitamin transporter (SMVT) and MCT1. It was shown that the prodrug is a substrate for both MCT1 and SMVT. The oral bioavailability of gabapentin following the administration of its prodrug was found to be 84.2% compared with 25.4% after a similar oral dose of gabapentin. Discovered and developed by XenoPort, gabapentin enacarbil was approved in the United States in 2011 for the treatment of moderate-to-severe primary restless legs syndrome (RLS) in adults and in June 2012 for the management of postherpetic neuralgia (PHN) in adults. Therapeutic effects of gabapentin enacarbil in RLS and PHN are attributable to gabapentin. The precise mechanism by which gabapentin is efficacious in RLS and PHN is unknown. In vitro studies have shown that gabapentin binds with high affinity to certain parts of voltage-activated calcium channels in the central nervous system. However, the relationship of this binding to the therapeutic effects of gabapentin enacarbil in RLS and PHN is unknown. The most common adverse reactions for adult patients with moderate-to-severe primary RLS and PHN receiving Horizant were somnolence/sedation, dizziness, headache, nausea and fatigue.

Lorazepam (brand name Ativan) is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. Lorazepam binds to an allosteric site on GABA-A receptors, which are pentameric ionotropic receptors in the CNS. Binding potentiates the effects of the inhibitory neurotransmitter GABA, which upon binding opens the chloride channel in the receptor, allowing chloride influx and causing hyperpolarization of the neuron. Studies in healthy volunteers show that in single high doses Ativan (lorazepam) has a tranquilizing action on the central nervous system with no appreciable effect on the respiratory or cardiovascular systems. Ativan (lorazepam) is readily absorbed with an absolute bioavailability of 90 percent. The mean half-life of unconjugated lorazepam in human plasma is about 12 hours and for its major metabolite, lorazepam glucuronide, about 18 hours. At clinically relevant concentrations, lorazepam is approximately 85% bound to plasma proteins. Lorazepam is rapidly conjugated at its 3-hydroxy group into lorazepam glucuronide which is then excreted in the urine. Lorazepam glucuronide has no demonstrable CNS activity in animal. Most adverse reactions to benzodiazepines, including CNS effects and respiratory depression, are dose dependent, with more severe effects occurring with high doses. Paradoxical reactions, including anxiety, excitation, agitation, hostility, aggression, rage, sleep disturbances/insomnia, sexual arousal, and hallucinations may occur. Small decreases in blood pressure and hypotension may occur but are usually not clinically significant, probably being related to the relief of anxiety produced by lorazepam.

Valproic acid (VPA; valproate; di-n-propylacetic acid, DPA; 2-propylpentanoic acid, or 2-propylvaleric acid) was first synthesized in 1882, by Burton. FDA approved valproic acid for the treatment of manic episodes associated with bipolar disorder, for the monotherapy and adjunctive therapy of complex partial seizures and simple and complex absence seizures and adjunctive therapy in patients with multiple seizure types that include absence seizures and for the prophylaxis of migraine headaches. The mechanisms of VPA which seem to be of clinical importance in the treatment of epilepsy include increased gamma-aminobutyric acid (GABA)-ergic activity, reduction in excitatory neurotransmission, and modification of monoamines. Recently, it was discovered that the VPA is a class I selective histone deacetylase inhibitor. This activity can be distinguished from its therapeutically exploited antiepileptic activity.

Diazepam is a benzodiazepine first discovered at Hoffman-La Roche in the late 1950s. Diazepam was approved by FDA for the treatment of anxiety disorders as well as for such conditions as skeletal muscle spasm, alcohol withdrawal syndrom and convulsions (under the most known brand Valium). The drug acts by binding to GABA-A receptors and potentiating GABA evoked current. Chronic diazepam use is associated with tolerance, dependence, and withdrawal.

Ethosuximide is a succinimide anticonvulsant, used in the treatment of epilepsy. Ethosuximide suppresses the paroxysmal three cycle per second spike and wave activity associated with lapses of consciousness which is common in absence (petit mal) seizures. The frequency of epileptiform attacks is reduced, apparently by depression of the motor cortex and elevation of the threshold of the central nervous system to convulsive stimuli. Binds to T-type voltage sensitive calcium channels. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channels is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. Ethosuximide is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.

Primidone is an anticonvulsant of the barbiturate class. It was introduced in 1954 under the brand name Mysoline by Wyeth in the United States. Mysoline, used alone or concomitantly with other anticonvulsants, is indicated in the control of grand mal, psychomotor, and focal epileptic seizures. It may control grand mal seizures refractory to other anticonvulsant therapy. Mysoline raises electro- or chemoshock seizure thresholds or alters seizure patterns in experimental animals. The mechanism(s) of primidone’s antiepileptic action is not known. Primidone per se has anticonvulsant activity, as do its two metabolites, phenobarbital and phenylethylmalonamide (PEMA). In addition to its anticonvulsant activity, PEMA potentiates the anticonvulsant activity of phenobarbital in experimental animals. Primidone itself doesn’t act on GABA-A receptors. It is active metabolite - phenobarbital primary acts via modulation of GABA -A receptors. The most frequently occurring early side effects are ataxia and vertigo. These tend to disappear with continued therapy, or with reduction of initial dosage. Occasionally, the following have been reported: nausea, anorexia, vomiting, fatigue, hyperirritability, emotional disturbances, sexual impotency, diplopia, nystagmus, drowsiness, and morbilliform skin eruptions.Granulocytopenia, agranulocytosis, and red-cell hypoplasia and aplasia, have been reported rarely. These and, occasionally, other persistant or severe side effects may necessitate withdrawal of the drug. Megaloblastic anemia may occur as a rare idiosyncrasy to Mysoline and to other anticonvulsants. The anemia responds to folic acid without necessity of discontinuing medication.