Sodium channel blocker · Grey Matter

A sodium channel blocker is an antiseizure drug that binds the voltage-gated sodium channels which produce the action potential, and it is the oldest and most widely used way of keeping neurons from firing in the long, fast runs that a seizure is made of.

Sodium channel blocker. A sodium channel blocker is an antiseizure drug that binds the voltage-gated sodium channels which produce the action potential, and it is the oldest and most widely used way of keeping neurons from firing in the long, fast runs that a seizure is made of.

Carbamazepine, phenytoin, lamotrigine and oxcarbazepine act this way, and lacosamide acts on the same channel by a related route. The trick that makes them usable is selectivity by activity. These drugs bind preferentially to the channel in its inactivated state, the state it enters for a moment after every spike. A neuron firing at a normal rate spends little time there and is barely affected; a neuron firing in a high-frequency burst leaves its channels inactivated again and again, the drug accumulates on them, and the burst falters. This is called use-dependent block.

They are first choices for focal epilepsies. Most focal seizures, including those that spread to both hemispheres, respond to them.

They can worsen some generalised epilepsies. Carbamazepine is ineffective for absence and myoclonic seizures and can aggravate them, which is why the epilepsy type has to be known before the drug is chosen.

Genes matter for safety. Carriers of the HLA-B*1502 allele, frequent in some Asian populations, have a much higher risk of severe skin reactions to carbamazepine, so testing before treatment is recommended where the allele is common.

Several of them also treat neuropathic pain and stabilise mood, a sign that cutting runaway firing is useful well beyond epilepsy.

A sodium channel blocker is a speed limit, and it only bites at speed.

By binding the channel in the state a fast-firing neuron keeps visiting, it trims bursts and leaves ordinary spikes nearly untouched.

Questions: How can a drug block sodium channels without stopping every normal spike? Drugs such as carbamazepine bind the voltage-gated sodium channel mainly in its inactivated state, the brief state it enters after opening for each spike. A neuron firing at an ordinary rate spends little time with its channels inactivated, so little drug binds; a neuron firing in a fast burst keeps its channels cycling through that state, the drug accumulates on them and fewer are ready for the next spike. The result, called use-dependent block, trims the long high-frequency runs that seizures are made of while leaving normal firing nearly intact.