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Tezampanel, TorreyPines Therapeutics' Lead Compound, Reduced Muscle Spasticity and Rigidity in Preclinical Study Conducted at University of California, San Diego

Data Suggest Potential for Treating Motor System Disorders

LA JOLLA, Calif., Oct. 17 /PRNewswire/-- Tezampanel, a novel small molecule currently in clinical development by TorreyPines Therapeutics, Inc. (Nasdaq: TPTX) for the treatment of acute migraine headache, was shown in an independent study to be effective in reversing or preventing muscle spasticity and rigidity in a rat model of spinal ischemia. These symptoms are commonly seen in Parkinson's disease, multiple sclerosis, cerebral palsy and other progressive motor system disorders caused by brain trauma or spinal cord injury.

In a study published in the October 17 issue of the Journal of Neuroscience, a team of international researchers found that tezampanel, identified in the study as NGX424, reduced muscle spasticity (stimulus-dependent increase in muscle tone) and rigidity (continuous stimulus-independent increase in muscle tone) in the hind legs of spinal ischemia-induced paraplegic rats. In humans with motor system disorders, muscle spasticity and rigidity, often combined with painful perception, can interfere with rehabilitation and daily activities.

The study was led by Michael P. Hefferan, Ph.D., and Martin Marsala, M.D., Anesthesiology Research Laboratory, Department of Anesthesiology, University of California, San Diego (UCSD). Neil Kurtz, M.D., President and Chief Executive Officer of TorreyPines Therapeutics, served as one of the study authors.

An AMPA/kainate receptor antagonist, tezampanel acts on glutamate receptors located in the brain and spinal cord. While essential to central nervous system function, excess glutamate production -- prompted by disease or injury -- can have pathological effects. In the study, tezampanel was found to block transmission of AMPA-evoked glutamate release and relieve symptoms of muscle spasticity and rigidity in treated rats without any detectable side effects such as respiratory depression or general sedation.

"Our research builds upon the growing appreciation for the role of increased glutamate release in both the triggering and the maintenance of several motor system disorders, and in the critical role that glutamate antagonists may have in reducing or reversing the damaging effects of the glutamate cascade," said Dr. Heffernan. "The potency of this compound in reducing spasticity and rigidity, as well as the minimal side effects after intrathecal delivery indicate that as a glutamate receptor antagonist, tezampanel may represent a unique and effective therapy for patients suffering with chronic spinal injury-induced spasticity and rigidity," said Dr. Marsala.

"To the best of our knowledge, tezampanel is the first AMPA/kainate receptor antagonist to be tested in humans and we believe these receptors represent an important new target for treating a variety of CNS diseases and disorders," said Dr. Kurtz. "While we remain committed to developing tezampanel for the treatment of acute migraine, our preclinical and clinical data demonstrate potential utility across a range of pain conditions, as well as diseases such as epilepsy and anxiety. These exciting results from the UCSD researchers further reinforce our belief in the versatility of this first-in-class compound."

Currently, patients experiencing muscle spasticity and rigidity are typically treated with muscle relaxants, tranquilizers or a GABA receptor agonist such as baclofen. Treatment may also include physical therapy regimens to prevent shrinkage or shortening of muscles. In the study, animals treated with tezampanel showed statistically significant (p=0.01) suppression of tonic electromyography activity as well as dose-dependent suppression of peripheral muscle resistance, flexion (abnormal contraction of limbs) of the ankle and dorsal plantar, motor evoked potentials and Hoffmann reflex (abnormal digit reflex).

About TorreyPines Therapeutics

TorreyPines Therapeutics, Inc. is a clinical stage biopharmaceutical company committed to the discovery, development and commercialization of novel small molecules to treat diseases and disorders of the central nervous system (CNS). Led by an accomplished management team, TorreyPines is leveraging novel drug targets and technologies to potentially deliver new CNS therapies for chronic pain, including migraine and neuropathic pain; and cognitive disorders, including cognitive impairment associated with schizophrenia and Alzheimer's disease. Further information is available at

This press release contains forward-looking statements or predictions. Such forward-looking statements include statements regarding the potential for tezampanel as a treatment for migraine and other pain indications, the potential for tezampanel to treat patients suffering from chronic and often progressive motor system disorders and the potential of the company's product candidates to treat certain diseases and disorders. Such statements are subject to numerous known and unknown risks, uncertainties and other factors, which may cause TorreyPines' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements, including whether any preclinical studies or clinical trials, either ongoing or conducted in the future, will prove successful, and if successful, whether the results can be replicated; whether safety and efficacy profiles of any of its drug candidates will be established, or if established, will remain the same, be better or worse in future clinical trials, if any; whether pre-clinical results will be substantiated by ongoing or future clinical trials, if any, or whether any of its drug candidates will be able to improve the signs or symptoms of their respective clinical indication; whether any of its drug candidates will support a filing for marketing approval, will be approved by the regulatory authorities, or if approved, will prove competitive in the market; or whether the necessary financing to support the company's drug development programs will be available. Actual results may differ materially from the above forward-looking statements due to a number of other important factors. These and other risks which may cause results to differ are described in greater detail in the TorreyPines Therapeutics' annual report on Form 10-K for the year ended December 31, 2006 as well as TorreyPines Therapeutics' subsequent filings with the Securities and Exchange Commission. TorreyPines Therapeutics undertakes no obligation to publicly release the result of any revisions to such forward-looking statements that may be made to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.

SOURCE TorreyPines Therapeutics, Inc.
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