The Latest on Tezampanel, a new Migraine Drug

Trials for the new migraine drug, Tezampanel (NGX424), are moving quickly ahead.  So it’s time to catch up on what this drug is, and who it might help.

Tezampanel is based on an emerging understanding of the role of glutamate (an amino acid) in pain.  Targeting glutamate receptors (either through antagonists like Tezampanel or through modulators like ADX10059) is a new concept that may help not only those with migraine, but also muscle spasticity, fibromyalgia, arthritis, diabetic neuropathy, epilepsy, and neuropathic pain in general.  It may also suppress symptoms of opioid medication withdrawal.

Why target Glutamate?

Glutamate is a key neurotransmitter.  It’s called an excitatory neurotransmitter, and is the one most commonly found in your body.

Glutamate has a number of functions in your body, which may include to ability to learn and memorize, and the transmission of pain signals.

During certain stages of the pain chain-reaction, glutamate gets very busy sending signals.  In certain people with chronic pain especially, there may be too much glutamate, inducing more pain than should be necessary.

Researchers are actually getting very excited about levels of glutamate, because this may be the key to understanding the mysterious chronic pain in many people.  Could it be that some people’s chronic pain could be "seen" by the levels of glutamate?  Better yet, could the pain chain reaction be stopped or slowed by controlling glutamate?

Glutamate does have a role in migraine.  It’s present in the trigeminal nerve (where migraine pain often radiates from).  It plays a role in cortical spreading depression (a brain "storm" that is a major part of a migraine attack), and seems to be key in causing central sensitization, where certain neurons in the spinal cord become sensitized, possibly causing increasing chronic pain.  (more about what happens during a migraine attack)

Enter Tezampanel

Tezampanel (also called NGX424) is a drug being developed by TorreyPines Therapeutics, based on research done at Johns Hopkins University.  It’s unlike any other drug in what it does.  In scientific terms, Tezampanel is an ionotropic glutamate receptor antagonist that targets the AMPA and kainate sub-type receptors.  Glutamate receptors receive glutamate and become activated – this drug is designed to interrupt the process.

There are actually two drugs here being tested, but we’ll get to the second in a moment.  Tezampanel itself is injected, and was compared with injections of Imitrex (sumatriptan).  It was found to work as well as Imitrex.  Symptoms that Tezampanel seems to help with:

  • pain (and excessive pain sensitivity)
  • nausea
  • sensitivity to light and sound
  • allodynia (sensitive/painful areas on the skin)

Tezampanel and NGX426

Another related drug in an earlier stage of testing is NGX426.  This is a "prodrug" of Tezampanel, which means that it causes Tezampanel to be formed in the body.

NGX426 is an oral drug, not an injection.  Last month (February 2009) a Phase I trial was completed, and so far so good (read the results of the this early trial).  NGX426 seems to have promise for relieving pain in migraine.

Side effects?

When a new drug comes out, there is always hope that many patients suffering from the side effects of something else may be able to make the switch.  How is Tezampanel looking regarding side effects?

So far the side effects seem to be fairly minimal.  Common ones seem to be:

  • pain at the injection site (of course this wouldn’t happen if you took NGX426 orally)
  • dry mouth
  • some other side effects in very few people may include dizziness and sleepiness

The next step

Tezampanel is heading into the last stages of testing.  NGX426 is farther behind, just heading into Phase II (of III).  TorreyPines Therapeutics is just putting together the funding it needs to carry out the next step.


Drugs coming out that are totally different than what has come before are especially interesting.  Not only may they help people who haven’t been helped, they may also lead to new treatments and breakthroughs.  When it comes to chronic pain, Tezampanel is one to watch.

From what we’ve seen so far, this drug may work well for some people who have been unable to take other types of migraine drugs due to side effects or other medical conditions.  It may also hold hope for those who have chronic pain conditions, including chronic migraine.

TorreyPines has more on Tezampanel and NGX426 here

Heads up from Ellen Schnakenberg

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9 comments… add one
  • Diana Lee Mar 12, 2009

    This research is very exciting. Just today I was reading a little something about it (in addition to your great article) and feeling like they might really be on to something. Here’s hoping they are!

  • James Mar 13, 2009

    Yes, I hope so too. I’m optimistic, and especially happy to see researchers pushing the limits and finding new ways to treat migraine.

  • Ellen Schnakenberg Apr 22, 2009

    Thanks for the mention James! Now that Telcagepant is having issues with preventive therapy trials, I am really hoping that Tezempanel doesn’t die on the side of the FDA approval road simply for lack of funding… I need that little light at the end of the tunnel to aim at. 🙂

  • James Apr 23, 2009

    There’s always light at the end of the tunnel – whether you can see it or not! 🙂

  • Jim from Tennessee Apr 26, 2009

    So any idea how long b4 this pain reliver is out on the market?

  • Bonnie Jul 19, 2013

    Very interesting info! Has anything happened with this drug or has it landed in the ash-heap? I was doing a search on this because so many of my migraines seem to originate with pain in my neck and back.

    I am currently on meds that affect my neurotransmitters and on anti-siezure meds. I have anywhere from 4-15 migraines a month.

    I have Ehlers-Danlos Syndrome and suffer from muscle spasticity, light and sound sensitivity, neck pain with cervical instability, and have neurological episodes including ringing in one of my ears, temporary loss of hearing in the same ear, trigeminal nerve pain, pain in my shoulder and arm, also odd sensations which resemble heart attack/stroke with nausea. I have complicated migraines with triggers such as food allergies, thunderstorms, severe pain episodes, crying, too much sunlight, etc, etc. I have a very sensitive brain that can only handle so much!

    I thought I had a stroke about a month ago, went to emergency, had a CT scan within a few hours, an ECG, an MRI the next day ( which had been previously scheduled), and nothing abnormal was found other than a few scattered hemangiomata, and only mild degenerative changes (found on the MRI); there were a few areas of mild central disc prominence in the C-spine but no evidence of cord compression. Although I am not convinced these “mild changes” are not causing me problems, considering gravity + hypermobility + other common degenerative problems can cause serious problems for people with EDS that others may not normally be affected by.

    Tezampanel sounds like it may help with all of my issues of pain/light/sound sensitivity, nausea, allodynia and nueropathy in dealing with migraine. May complement the other drugs I am already on.

    Does it target migraine pain specifically or pain and nausea in general?

  • Esme Oct 17, 2015

    Hey Dave,My wife gets migraines. The real ones pain, naesua, super-sensitive sense of smell, very sensitive to light, etc. We take some high quality supplements which seem to help. They’re not gone, but they’re better than they used to be. Less frequent, too. So I’ll add a vote to the idea that high quality nutrition can help here.

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