By Andrew N. Wilner, MD
SALT LAKE CITY, Utah -- September 24, 2008 -- Tezampanel, an AMPA/kainate receptor antagonist, was more effective in treating acute migraine attacks compared with placebo, according to a recent study presented at the American Neurological Association (ANA) 133rd Annual Meeting.
Lead author Neil Kurtz, MD, Golden Living, Fort Smith, Arkansas, presented the study. Dr. Kurtz was with TorreyPines Therapeutics, Inc., when the single-dose, placebo-controlled, double-blind study was conducted.
In his presentation on September 23, Dr. Kurtz explained that AMPA/kainite receptors are ion-gated inotropic receptors that regulate sodium and calcium flow across the neuronal cell membrane. Tezampanel can block these receptors and inhibit this ionic flow. AMPA/kainate receptors are important in the phenomenon of central sensitisation in the brain and spinal cord, according to Dr. Kurtz. In migraine patients, the number of AMPA/kainate receptors increase in the trigeminal ganglion.
Central sensitisation appears to play a role in neuropathic pain, migraine headache, chronic diabetic neuropathy, herpetic and HIV neuropathy, and some types of chronic cancer pain. The drug is not associated with tachyphylaxis, making it a good potential drug for chronic treatment, he said.
In their study, the researchers administered 1 dose of tezampanel 40 mg or placebo subcutaneously to 306 patients with moderate to severe migraine.
Results showed that tezampanel was more effective than placebo in eliminating migraine pain at 2 hours (P = .011).
At baseline, 58% of the patients in the tezampanel group had cutaneous allodynia compared with 56% in the placebo group. After tezampanel treatment, 83.3% of the patients with cutaneous allodynia had pain relief, compared with 59.5% on placebo.
This is the first study to demonstrate effectiveness of an AMPA/kainate antagonist in migraine patients with cutaneous allodynia. Effectiveness of tezampanel in the presence of cutaneous allodynia is important because many of these patients are refractory to triptan treatment.
According to Dr. Kurtz, future studies will include testing of an oral form of tezampanel, which will soon be available. Phase 3 studies are currently under consideration.
"Tezampanel has the potential to be a very important new medication for the management of pain because of its unique mechanism of action," Dr. Kurtz concluded.
[Presentation title: Tezampanel, an AMPA/Kainate Antagonist, Is Effective in Treating Migraine in the Presence of Cutaneous Allodynia. Abstract M-98]
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