In a new report, researchers for the Columbia University Medical Center (CUMC) have cracked the code of how the new antiepileptic drug, named Perampanel, works to help people with epilepsy. If further studies verify and support these findings, it should open the door for pharmaceutical manufacturers to produce improved medications that are safer and more effective than those already on the market. This would be a significant breakthrough as current treatments have no effect on about a third of those with this disorder.
Epilepsy, also known as seizure disorder, is the fourth most common neurological disorder, trailing only migraine, stroke, and Alzheimer’s disease. It is more prevalent in children and older adults and it affects 1 in every 26 people.
How AMPA Inhibitors Affect Epilepsy
The study, “Structural bases of noncompetitive inhibition of AMPA subtype ionotropic glutamate receptors by antiepileptic drugs,” focused on the structure and function of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors in the central nervous system. AMPA receptors are responsible for rapid synaptic transmission in the CNS. However, previous clinical research into the efficacy of Perampanel and other AMPA inhibitors have been hindered by serious side effects.
|The process behind antiepileptic drugs. Source: nih.gov|
Taking a unique approach, the team of scientists led by Dr. Alexander I. Sobolevsky, professor of biochemistry and molecular biophysics at CUMC, employed crystallography to learn how Perampanel and two other AMPA inhibitors interacted with the AMPA receptors in rats (whose receptors are essentially identical to humans). They found that these drugs closed the channel that allows ions to pass into a cell and trigger an electrical impulse, thereby preventing the transmission of electrical signals. In addition, they also located where the inhibitors bind to the receptor.
The belief is that now that the process behind how Peramapanel and other antiepileptic drugs work has been revealed, this information will provide the scientific foundation for manufacturers to develop medications that are selective for AMDA receptors in order to provide safer and more effective treatment of epilepsy and the condition’s associated seizures.