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How anti-seizure medication works

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How anti-seizure medication works

For most people with epilepsy, the treatment for their seizures includes anti-seizure medication (ASM), previously called anti-epileptic drugs or AEDs. But what do these drugs do? Here we look in greater technical detail at how ASM works, what it does, and doesn't do.

What it does (and doesn’t do)?

ASM does not cure epilepsy or treat the reason why epilepsy has started. It is taken to try and stop the symptoms of epilepsy – the seizures. It aims to stop seizures from happening. Except for emergency medication, most ASM does not stop a seizure once it has started. 

How ASM gets to the brain

To work, drugs need to get from where you take them to where they start to work. They need a route to get there and a waste-removal system to get rid of them afterwards.

The route of administration

There are various ways medications are taken -  by mouth, by injection (into the vein, muscle, or just under the skin), or by suppository (into the bottom). ASM is usually taken orally (by mouth), and in the form of tablets, capsules, liquids and syrups.

Absorption in the stomach

Once swallowed, ASM goes into the stomach. Digestive juices in the stomach help to break down food and, in this case, the tablets containing the medication.

The tablets break down, releasing the medication which can then pass through the wall of the gut into the bloodstream (absorption), and be distributed around the body. The quicker the medicine gets into the bloodstream the quicker it can get to work. 

Once the medication is absorbed it can act and do the job it is supposed to.

Once in the bloodstream, ASM is carried to the site of action: in this case, the brain.

How well and quickly the drugs get to their site of action depends on how well the part of the body is supplied with blood, and how easily the drug gets from the blood stream into the part of the body.

Although the brain has a good supply of blood, there is a barrier between the blood and the brain that helps protect the brain from infections and toxic chemicals. This means that drugs do not pass easily into the brain. 

Once drugs have played their active role, they start to break down (metabolise) so that they can be excreted from the body (passed out through the digestive tract, like food and drink, or in the urine). How long before ASM starts to be metabolised varies from one to another and is referred to as their half-life.

To be excreted in the urine, ASM has to be broken down so that it can dissolve in water, and then the kidneys can get rid of it. Some ASMs become inactive when they are metabolised.

Most ASMs are metabolised in the liver (hepatic metabolism) where they are changed into water-soluble metabolites with the help of different enzymes. Some ASMs – gabapentin, vigabatrin, levetiracetam and pregabalin, are not metabolised, not affected by hepatic enzymes, and they are excreted in the same form in the urine.

How ASM stops seizures?

ASM makes the brain less likely to have seizures by altering and reducing the excessive electrical activity (or excitability) of the neurones that normally cause a seizure. Different ASMs work in different ways and have different effects on the brain. How exactly some ASMs work is still not fully understood. 

Targets in the brain

There are several different ways in which ASM stops seizures from happening, by working on particular targets in the brain. ASM may affect the neurotransmitters responsible for sending messages, or attach itself to the surface of neurones and alter the activity of the cell by changing how ions (chemicals found in the body that have an electrical charge), flow into and out of the neurones.

See our information on Neurones.

We will look at four targets (although there are others):

  • sodium ion channels
  • calcium ion channels
  • the GABA system and receptor agonists
  • glutamate receptor antagonists.

Sodium ion channels

Sodium channels are the parts of the neurone that affect how electrical signals or messages are passed along the length of a neurone. 'Action potentials' are events that cause the cell membrane of the neurone to depolarize and repolarize (when the balance of ions inside and outside the neurone changes, which causes the electrical charge of the neurone to change). This is because they change the amount of ions inside and outside the cell, which then changes the electrical charge of the cell. This is how messages travel along a neurone”. Sodium channels affect how ‘excitable’ neurones are and how easily messages are sent from one brain cell to another.

Some ASMs (such as phenytoin, lamotrigine and carbamazepine) work by affecting the sodium channels of neurones. ASM that binds or attaches itself to the sodium channels affects how ions flow through the channels, and stops the channel becoming activated or creating an action potential. This slows down how fast and how well the sodium channels work, which effectively stops the neurone from sending repeated messages.

Calcium ion channels

Calcium ions, like sodium ions, are involved in sending electrical messages through the brain. Calcium channels are particularly involved with sending a message from one neurone to another, by affecting the release of neurotransmitters (chemicals that help to send messages from one neurone to another) across the synapse, where two neurones meet, and by affecting the movement of calcium ions in the receiving neurone.

ASM that targets calcium channels (such as zonisamide and topiramate) works by blocking the calcium channels. This prevents messages being sent across the synapse from one neurone to another either by stopping the release of neurotransmitters, or by preventing calcium entering the second neurone.

One particular type of calcium channel, called the T-type channel, is involved in keeping the normal rhythm of brain activity. This channel is also involved in the specific brain activity that happens in absence seizures. ASM that specifically targets, and blocks, the T-type calcium channel (such as ethosuximide), works specifically on reducing absence seizures.

GABA system and receptor agonists

GABA (gamma amino butyric acid) is a type of inhibitory neurotransmitter in the brain, which effectively stops brain messages from continuing to be sent (switches messages off). GABA helps chloride ions pass into neurones, which affects the resting membrane potential of the cell and makes it difficult for the neurone to send messages.

ASM that works on the GABA system and its receptors are agonists (a substance that helps another substance to work better), and effectively increases the movement of chloride into cells, and increases the 'switching off' of messages.

ASM such as gabapentin works by increasing the production of GABA, and sodium valproate and vigabatrin work by decreasing the breakdown of GABA, both of which result in an increased amount of GABA.

ASM such as benzodiazepines (including clonazepam and clobazam) increases how often GABA receptors open, and barbiturates (such as phenobarbitone) increase how long the receptors are open for, again affecting the release and movement of GABA.

Increasing the making of GABA, reducing its breakdown, and increasing its movement, all results in increases its inhibitory effect (more GABA means more prevention of messages being sent).

Glutamate receptor antagonists

Glutamate is a type of amino acid, and is a major excitatory neurotransmitter in the brain. Messages are sent from one neurone to another in excitation, due to the movement of sodium and calcium ions into cells, and potassium out of cells. This movement of ions through the cell membranes is helped by glutamate, which binds to different receptors on the cell membrane.

Drugs that bring about and prevent glutamate uptake (antagonists) stop glutamate from helping the movement of ions through the cell membrane and so prevent the spread of the messages from one neurone to another.

The ASM perampanel works specifically on glutamate receptors, while some other ASM (such as topiramate) works on glutamate receptors as well as other targets.

Different ASMs use different targets, or a combination of targets. For some it is known which targets they use, but for others it is not yet known.

Information reviewed January 2020

Taken from our 'a closer look - how anti-epileptic drugs work' factsheet