Mechanisms Behind Epilepsy Drugs Uncovered

Perampanel is an antiepileptic that inhibits AMPA receptors, but can cause side effects in patients.

Scientists have recently discovered how new antiepileptics work by inhibiting a brain receptor, a discovery that could lead to safer and more effective treatments.

Common antiepileptics can be ineffective for approximately 30% of patients with epilepsy. It has also been shown that some epilepsy treatments may cause psychotic disorders, especially in women and patients with temporal lobe epilepsy, making the need for safer medications critical.

Novel treatments affect an alternative target, such as AMPA receptors, in hopes of creating a treatment effective for more patients. The AMPA receptors transmit electrical signals in the brain, and play a role in propagating seizure.

The drug is thought to prevent seizures by blocking electrical spread in the brain. Perampanel is the only AMPA receptor-inhibitor that has received FDA approval, but its use is limited due to side effects, according to a study published in Neuron.

“The problem is that AMPA receptors are heavily involved in the central nervous system, so if you inhibit their function, you cause an array of unwanted effects,” said study leader Alexander I. Sobolevsky, PhD. “If we hope to design better drugs for epilepsy, we need to learn more about the structure and function of these receptors.”

In the study, scientists used crystallography to determine how perampanel and 2 inhibitors affect AMPA receptors in rats. Rat AMPA receptors are almost identical to human receptors, according to the study.

“Our data suggest that the inhibitors wedge themselves into the AMPA receptor, which prevents the opening of a channel within the receptor,” said Dr Sobolevsky.

Ions cannot pass into the cell to trigger an electrical signal when the channel is closed, which can inhibit seizures, the researchers wrote. These findings can provide drug makers with a way to create more highly-selective medications for AMPA receptors.

These medications could provide patients with a safer and more effective treatment, the study concluded.