ANTI-SEIZURE DRUGS: USES, TYPES AND MECHANISM OF ACTION - MEDICINE - 2025

The antiepileptic drugs are mainly used for seizures, some psychopathological disorders such as bipolar disorder and, above all, for neuropathic pain. They are sometimes called antiepileptic or anticonvulsant drugs.

There are classic or first-generation anti-seizure drugs and second-generation ones. The newer ones tend to have fewer side effects, although both types are generally equally effective.

These drugs work by eliminating the excessive electrical activity of neurons that is typical of seizures. They also help prevent impaired activity from spreading through the brain. They also reduce pain and produce relaxation through different mechanisms.

The first anti-seizure drug was bromide, which emerged in 1857. At that time it was thought that epilepsy arose from excessive sexual desire. They found that bromide was effective against epilepsy, but it caused impotence and affected behavior.

Later, in 1910, they realized that phenobarbital, which was used to induce sleep, had anticonvulsant activity. Thus, it became the drug of first choice for a long time.

In 1930, phenytoin was developed to treat epileptic seizures without producing as much sedation.

What are anti-seizure drugs for?

Anti-seizure drugs are often used for different types of epilepsy, for neuropathic pain and certain psychopathological disorders. Some of them have also been helpful in reducing withdrawal symptoms or drug addiction problems.

Epilepsy

It has been shown that approximately 70% of patients with epilepsy manage to control their seizures with anticonvulsant drugs. However, these drugs act on the symptoms and not on the origin of the disease, therefore, they cannot cure epilepsy, and the treatment must be taken for a long time.

Neuropathic pain

Anti-seizure drugs were initially widely used for people with epilepsy. Later, they discovered that it could ease pain caused by nerve damage.

Nerves can be injured by trauma, compression, diseases, surgeries… Thus, they are activated when they should not send pain signals without a useful purpose. This is called neuropathy.

The exact mechanism of action of anti-seizure drugs is not fully understood. These drugs appear to prevent the transmission of pain signals from damaged or sensitive nerves.

Also, each type of drug works better under some conditions than others. For example, carbamazepine is widely used to treat trigeminal neuralgia, a condition in which severe pain is experienced in the face.

Psychopathological disorders

Anti-seizure drugs are also widely used for mental disorders such as bipolarity, borderline personality disorder, or anxiety disorders.

These drugs have been shown to treat acute mania, aggressive and impulsive behaviors associated with personality disorders, eating disorders or agitation related to dementia. One of the drugs used for this is oxcarbazepine.

Types of anticonvulsant drugs

There are two main types of anti-seizure: the classic or first generation and the second generation. Each of them has better effects under specific conditions. The latter were created with the aim of reducing the side effects of the former.

First Generation Anticomestic

These drugs act mainly by blocking sodium or calcium channels, reducing neuronal activity.

Among the classic drugs, carbamazepine stands out. This is the most studied anticonvulsant in the treatment of neuropathic pain. It works by blocking voltage-gated sodium channels, stabilizing the activity of neuronal membranes. On the other hand, it blocks the NMDA receptor, which is activated by sodium and calcium.

Its most common side effects are drowsiness, nausea, vertigo, diplopia (double vision), etc.

Other classic anticonvulsants are phenytoin and valproic acid. The former also stabilizes neuronal membranes. In addition, it inhibits the release of calcium and calmodulin, and modifies the conductance of potassium.

It is not usually used due to its many interactions with other substances and its side effects. Among these have been found dizziness, ataxia, sedation, dysarthria (problems to articulate language), alterations in cognitive functions, acne, arrhythmias, etc.

On the other hand, valproic acid seems to act on the GABAergic system, that is, enhancing the inhibition produced by GABA. In addition, it blocks the transmission of excitatory substances such as aspartate and glutamate.

Its side effects include nausea, vomiting, tremor, weight gain, and less commonly liver disorders and pancreatitis.

Second Generation Anticomestic

The new anticonvulsant drugs have a more marked action on neurotransmitters, increasing the action of GABA in different ways. They also have antiglutaminergic effects. However, they operate at more levels that are not yet fully understood.

Mechanism of action

There are multiple mechanisms of action such as GABA receptor agonists, which are drugs that mimic this neurotransmitter by binding to its specific receptors. These include clobazam, clonazepam (which is a benzodiazepine that also works to treat myoclonus and anxiety), phenobarbital, and primidone.

On the other hand, there are drugs that inhibit GABA reception, that is, GABA is absorbed by cells for subsequent elimination. The most common is tiagabine, which was introduced into clinical practice around 1998.

There are also inhibitors of GABA transaminase, an enzymatic process that metabolizes this neurotransmitter. These anti-seizure drugs inhibit the activity of the enzyme to increase the extracellular concentration of GABA. An example is bigamatrin. However, its use is restricted by its toxicity levels. In fact, it has not been approved in the United States.

On the other hand, other drugs potentiate the action of the enzyme glutamic acid decarboxylase (GAD), which converts glutamate (the main excitatory neurotransmitter) into GABA. Within this type are gabapentin, pregabalin and valproate.

The latter is one of the most widely used anticonvulsant drugs in the world, especially for generalized epilepsies and partial seizures.

Finally, there are drugs whose main effect is to block glutamate, which is an excitatory neurotransmitter. These include felbamate, which has very limited use due to its side effects (aplastic anemia and liver failure), and topiramate.

Other drugs with different or poorly understood mechanisms of action include levetiracetam, brivaracetam, and rufinamide.

The choice of each anti-seizure drug will depend on the individual characteristics of each patient (age, symptoms, etc.).

The newer anticonvulsants tend to have fewer side effects, therefore they are often used as a first option. If they are not effective for the patient, older ones can be prescribed.

References

1. Alba, NC (2008). Anticonvulsants in the therapeutics of impulsivity. Actas Esp Psiquiatr, 36 (3), 46-62.
2. Anticomiciales. (sf). Retrieved on April 16, 2017, from Neurowikia: neurowikia.es.
3. Anticonvulsant. (sf). Retrieved on April 16, 2017, from Wikipedia: en.wikipedia.org.
4. Anti-seizure medications: Relief from nerve pain. (sf). Retrieved on April 16, 2017, from Mayo Clinic: mayoclinic.org.
5. Epilepsy Drugs to Treat Seizures. (sf). Retrieved on April 16, 2017, from WebMD: webmd.com.
6. Ochoa, J. (March 8, 2016). Antiepileptic Drugs. Obtained from Medscape: emedicine.medscape.com.
7. Saíz Díaz, R. (2004). Antiepileptics: Contribution of new drugs. Obtained from Therapeutic Information of the National Health System: msssi.gob.es.
8. Seizure Medications. (sf). Retrieved on April 16, 2017, from RxList: rxlist.com.