[Info] Perampanel ???

[John Sturgis]

I have learned that glutamate receptors have been discovered to have a role in the onset of epilepsy.I know that anti-epileptic drug Perampanel is SET UP as an orally administered, highly selective non-competitive AMPA-type glutamate receptor antagonist. My nocturnal seizures are under control with an anti-epileptic drug-GERD diet combo. I agree that when my personal glutamate level is high it creates excitotoxicity which is the pathological process in which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. I know that Perampanel has not been approved yet by the FDA but I was wondering what anyones thoughts are on this new approach type drug. By the way, for the first time, I had an active positive discussion, in April 2011, with my neurologist at Beth Israel Hospital - Boston on the affects that msg, sweeteners, etc. have on my seizure occurrences.Thanks again, John Sturgis

[Cint]

An article from medscape.com

Perampanel Add-On Reduces Partial-Onset Seizures
First in Class

Perampanel, also known as E2007, is a first-in-class, highly selective, noncompetitive antagonist for alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid. Most epilepsy drugs target channel activity, but this agent uses a different approach and focuses on excitatory damage.

"This is a completely different mechanism," Dr. French said. She speculates that it may also prove to be disease-modifying.

Asked by Medscape Medical News to comment, Joseph Sirven, MD, from the Mayo Clinic in Scottsdale, Arizona, said he is also excited about this novel approach. "Perampanel is approaching epilepsy from a new direction and I think this will help open the door to other agents as well."

Marc Nuwer, MD, from the University of California at Los Angeles, said he agrees. "I'm really happy to see a new category of drugs. We've had a dozen new agents emerge over the last 20 years, but many of them have been slight tinkerings of already established drugs. This is actually a new category and a step forward."

Top-line positive results from the first perampanel trial, known as Study 306, were unveiled in August 2010. These new high-dose numbers are from Study 304.

The trial included 387 people with uncontrolled epilepsy in the United States, Canada, and Latin America. Patients were already taking 1 to 3 antiepileptic drugs.

Investigators assigned patients to receive perampanel once daily, either 8 or 12 mg or placebo, in addition to their regular therapy. Treatment continued for 19 weeks.

The prespecified primary outcome for US regulators was percentage change in seizure frequency per 28 days.

The prespecified primary outcome for European regulators was responder rate of 50% or greater reduction in seizure frequency.

Patients who took the 12-mg dose had a 14% reduction in seizures in a 28-day period compared with those who took placebo. Those receiving the 8-mg dose reduced their seizure frequency by nearly 6% compared with those receiving placebo.

Shows what the doctors are saying about this new type of drug. IMO, it's worth a try for those whose seizures are not controlled.

BTW, here is another website about glutamate as a neurotransmitter:
http://www.neurotransporter.org/glutamate.html

[Nakamova]

Hi John --

Glutamate is an "excitatory" neurotransmitter, so anything that's an antagonist to its receptors can potentially play a role in seizure control. Some older anti-epileptic drugs (such as phenobarbital) also work as glutamate receptor antagonists, though perhaps not the "highly selective non-competitive AMPA-type" that's mentioned for Perampanel. It looks like it's still in the early stages of the approval process, so it may be awhile before it's available to patients.


It's nice to hear that your Beth Israel neurologist is receptive. My Beth Israel neurologist has been less so, though I've worked hard over the last ten years to break her in...

[epileric]

Here's another study on Glutamate and Glutamine in the Brain

[John Sturgis]

I was showing my neurologist that my 6 month daily seizure occurence diary only showed seizures when I had an accidental intake of msg/sweetener. The doctor did listen to what I said about exitotoxins & there possible affect on me. Our discussion was not extensive but it's a start. I do believe that the neurological field is on the cusp of understanding how glutens & sweeteners can cause seizures. I have had seizures all my life but under control now.