Researchers at Columbia University Medical Center have described, in detail, the structure and function of a type of receptor called the AMPA receptor. This plays an important role in the activation of neurons, but in epilepsy it contributes to seizure spread.Currently there is only one approved drug, known as perampanel, that inhibits AMPA receptors to try and stop seizures. However, because AMPA receptors are present throughout the central nervous system, blocking them produces unwanted effects. There is a need for new drugs that are more targeted in their action (ideally working only where the epileptic activity is), and hopefully more effective.To develop these, researchers first need to know exactly how AMPA receptors are formed and work, and precisely how compounds like perampanel inhibit them.The team at Columbia University took AMPA receptors from rodents and used a technique called crystallography to map their 3D structure. They also managed to pinpoint where on the AMPA receptor perampanel and two other similar drugs bind, thereby inhibiting/silencing neurons.Dr Alexander Sobolevsky, Senior Author, said: “Our data suggest that the inhibitors wedge themselves into the AMPA receptor, which prevents the opening of a channel within the receptor. When that channel is closed, ions cannot pass into the cell to trigger an electrical signal.”Existing antiepileptic drugs (AEDs) are effective in preventing seizures in approximately two thirds of people with epilepsy. The remaining third, however, will not respond to medication alone. A new, more selective, AMPA receptor inhibitor would potentially offer more people with epilepsy the chance of seizure freedom. It might also be more effective than current AEDs, with fewer side effects.The study was published in the scientific journal Neuron.Author: Dr Özge ÖzkayaClick here for more articles about brain science including genetics.
2019-10-26T22:52:16+01:00September 9th, 2016|