Researchers at Columbia University Medical Centre (CUMC) have identified how anti-epileptic drug Perampanel blocks AMPA receptors in the brain that help in the transmission of electrical signals and play a role in the development of seizures.
Epilepsy is a group of neurological diseases characterised by epileptic seizures.
Better understanding of how epilepsy drugs work could lead to the development of more effective drugs with fewer side effects.
The scientists have studied the effects of Perampanel on rat AMPA receptors, which are almost similar to human receptors.
A technique called crystallography was used to determine how the drug and two other inhibitors interact with the AMPA receptors to stop transmission of electrical signals.
Researchers said they were able to pinpoint exactly where the drugs bind to AMPA receptors.
CUMC biochemistry and molecular biophysics professor Alexander I. Sobolevsky said: “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.
“If we hope to design better drugs for epilepsy, we need to learn more about the structure and function of these receptors.”
Though Perampanel is the only FDA-approved drug that targets AMPA receptors, the drug's clinical use has been limited as it is associated with significant side effects.
According to the study, the most commonly used anti-epilepsy drugs are ineffective for about 30% of people with seizure disorders.
Image: Extracellular portions of transmembrane helical segments of AMPA receptor (blue) contribute their amino acid side chains (yellow sticks) to form the binding site of the antiepileptic drug Perampanel (green). Photo: courtesy of Laboratory of Alexander Sobolevsky, PhD/Columbia University Medical Centre.
