ATC Group: N03A Antiepileptics

Brivaracetam displays a high and selective affinity for synaptic vesicle protein 2A (SV2A), a transmembrane glycoprotein found at presynaptic level in neurons and in endocrine cells. Although the exact role of this protein remains to be elucidated it has been shown to modulate exocytosis of neurotransmitters.

Cannabidiol is indicated for the treatment of seizures associated with Lennox‑Gastaut syndrome (LGS), Dravet syndrome (DS), or tuberous sclerosis complex (TSC) in patients 1 year of age and older.

Carbamazepine is a derivative of dibenzazepine. It belongs to the pharmaceutical class of antiepileptic, neurotropic and psychotropic drugs. Carbamazepine helps control the transmission of messages from the brain to the muscles.

Cenobamate is a small molecule with a dual mechanism of action. It is a positive allosteric modulator of subtypes of the γ-aminobutyric acid (GABAA) ion channel, that does not bind to the benzodiazepine binding site. Cenobamate has also been shown to reduce repetitive neuronal firing by enhancing the inactivation of sodium channels and by inhibiting the persistent component of the sodium current.

Clonazepam exhibits pharmacological properties which are common to benzodiazepines and include anticonvulsive, sedative, muscle relaxing and anxiolytic effects. Animal data and electroencephalographic investigations in man have shown that clonazepam rapidly suppresses many types of paroxysmal activity including the spike and wave discharge in absence seizures (petit mal), slow spike wave, generalised spike wave, spikes with temporal or other locations as well as irregular spikes and waves.

Eslicarbazepine and its metabolites stabilise the inactivated state of voltage-gated sodium channels, precluding their return to the activated state and thereby preventing repetitive neuronal firing. Therefore eslicarbazepine is indicated as adjunctive therapy in adults with partial-onset seizures with or without secondary generalisation.

Ethosuximide is an anti-epileptic of the class of succinimides that apparently exerts multiple mechanisms of action. The activity of ethosuximide in absence type epilepsy seems to rely primarily on the inhibition of T-type calcium channels in the thalamus.

Ethotoin is a hydantoin anticonvulsant with anti-epileptic activity. Ethotoin exerts an antiepileptic effect without causing general central nervous system depression. The mechanism of action is probably very similar to that of phenytoin.

Fenfluramine is a serotonin releasing agent, and thereby stimulates multiple 5-HT receptor sub-types through the release of serotonin. Fenfluramine may reduce seizures by acting as an agonist at specific serotonin receptors in the brain, including the 5-HT1D, 5-HT2A, and 5-HT2C receptors, and also by acting on the sigma-1 receptor. The precise mode of action of fenfluramine in Dravet syndrome and Lennox-Gastaut syndrome is not known.

Ganaxolone is a methyl analogue of the endogenous neurosteroid allopregnanolone. Ganaxolone is a neuroactive steroid that positively and allosterically modulates gamma-aminobutyric acid type A (GABA_A) receptors in the CNS by interacting with a recognition site that is distinct from other allosteric GABA_A receptor modulators. Its anticonvulsant effects are thought to result from this modulation of GABA_A receptor function providing constant, or tonic, modulation of GABA-mediated inhibitory neurotransmission.

Lacosamide is a functionalised amino acid. The precise mechanism by which lacosamide exerts its antiepileptic effect in humans remains to be fully elucidated.

Lamotrigine is a use and voltage dependent blocker of voltage gated sodium channels. It inhibits sustained repetitive firing of neurons and inhibits release of glutamate (the neurotransmitter which plays a key role in the generation of epileptic seizures).

Levetiracetam, is a pyrrolidone derivative, chemically unrelated to existing antiepileptic active substances. Levetiracetam induces seizure protection in a broad range of animal models of partial and primary generalised seizures without having a pro-convulsant effect. The primary metabolite is inactive.

Mesuximide is a succinimide with anticonvulsant properties. Although the exact mechanism of action of methsuximide is unclear, it is thought to increase the seizure threshold and suppress the paroxysmal three-cycle-per-second spike-and-wave pattern seen with absence (petit mal) seizures.

Methylphenobarbital is a barbiturate derivative and is used primarily as an anticonvulsant, but also as a sedative and anxiolytic. It is the N-methylated analogue of phenobarbital and has similar indications, therapeutic value, and tolerability.

The pharmacological activity of oxcarbazepine is primarily exerted through the metabolite (MHD). The mechanism of action of oxcarbazepine and MHD is thought to be mainly based on the blockade of voltage-sensitive sodium channels.

Perampanel is a first-in-class selective, non-competitive antagonist of the ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor on post-synaptic neurons. Glutamate is the primary excitatory neurotransmitter in the central nervous system and is implicated in a number of neurological disorders caused by neuronal overexcitation. The precise mechanism by which perampanel exerts its antiepileptic effects in humans remains to be fully elucidated.

Phenobarbital has sedative effects and has some protective action against all varieties of human partial and generalised epilepsy, with the exception of absence seizures. Phenobarbital is also effective in preventing seizures in the corresponding experimental animal models of epilepsy.

Phenytoin is effective in various animal models of generalised convulsive disorders, reasonably effective in models of partial seizures but relatively ineffective in models of myoclonic seizures. It appears to stabilise rather than raise the seizure threshold and prevents spread of seizure activity rather than abolish the primary focus of seizure discharge.

Primidone is an anticonvulsant. Although the precise mode of action of primidone is unknown, in common with other anticonvulsants, effects on the neuronal membrane particularly with respect to alteration of ionic fluxes are likely to play a fundamental role.

In vitro studies indicate that retigabine acts primarily through opening neuronal potassium channels. This stabilises the resting membrane potential and controls the sub-threshold electrical excitability in neurons, thus preventing the initiation of epileptiform action potential bursts. The mechanism of action of retigabine on potassium channels has been well documented, however other mechanisms by which retigabine may assert an antiepileptic effect have yet to be fully elucidated.

Rufinamide is an anticonvulsant medication. Rufinamide modulates the activity of sodium channels, prolonging their inactive state.

Stiripentol potentiates the efficacy of other anticonvulsants, such as carbamazepine, sodium valproate, phenytoin, phenobarbital and many benzodiazepines, as the result of pharmacokinetic interactions. The second effect of stiripentol is mainly based on metabolic inhibition of several isoenzymes, in particular CYP450 3A4 and 2C19, involved in the hepatic metabolism of other anti-epileptic medicines.

Sultiame is indicated as an anticonvulsant for behavioural disorders associated with epilepsy; hyperkinetic behaviour; temporal lobe epilepsy; myoclonic seizures; grand mal attacks; Jacksonian seizures.

Tiagabine is an anti-epileptic drug. Tiagabine is a potent and selective inhibitor of both neuronal and glial GABA uptake, which results in an increase in GABAergic medicated inhibition in the brain.

Topiramate is classified as a sulfamate-substituted monosaccharide. The precise mechanism by which topiramate exerts its antiseizure and migraine prophylaxis effects are unknown.

Trimethadione is an antiepileptic agent. Trimethadione has been shown to prevent pentylenetetrazol-induced and thujone-induced seizures in experimental animals; the drug has a less marked effect on seizures induced by picrotoxin, procaine, cocaine, or strychnine. Unlike the hydantoins and antiepileptic barbiturates, trimethadione does not modify the maximal seizure pattern in patients undergoing electroconvulsive therapy.

Valproic acid is anti-convulsant. The most likely mode of action for valproate is potentiation of the inhibitory action of gamma amino butyric acid (GABA) through an action on the further synthesis or further metabolism of GABA.

Vigabatrin is a selective irreversible inhibitor of GABA transaminase, the enzyme responsible for the breakdown of GABA (gamma aminobutyric acid). Vigabatrin increases the concentration of GABA, the major inhibitory neurotransmitter in the brain.

Zonisamide is a benzisoxazole derivative with antiepileptic and anticonvulsant activity. The mechanism of action of zonisamide is not fully elucidated, but it appears to act on voltage-sensitive sodium and calcium channels, thereby disrupting synchronised neuronal firing, reducing the spread of seizure discharges and disrupting subsequent epileptic activity.