Source: Pain Therapeutics, Inc Press Release
Date: 16 October 2006

Oxytrex(TM) Mechanism of Action Further Elucidated

New Data in Peer-Reviewed Journal and Neuroscience Meeting

SOUTH SAN FRANCISCO, Calif., Oct. 16 /PRNewswire-FirstCall/ -- Pain Therapeutics, Inc. (Nasdaq: PTIE - News), a biopharmaceutical company, today announced that a team of researchers, led by Prof. H.-Y. Wang of CUNY Medical School, has published further evidence for the unique mechanism of action of ultra-low-dose (ULD) opioid antagonists. Their data are also being presented today at the 36th Annual Meeting of the Society for Neuroscience (Atlanta), a venue of over 30,000 scientists and physicians dedicated to understanding how the brain works.

In a new article published in Journal of Neurobiology, the researchers describe how chronic opioid use leads to excitatory cell signaling. This excitatory signaling leads to a downstream cascade of events that underlie opioid tolerance and dependence. The researchers demonstrated that opioid excitatory signaling is prevented by co-treatment with an ULD opioid antagonist. Blocking this excitatory cell signaling is key to minimizing opioid tolerance and physical dependence. Pain Therapeutics' novel painkiller, Oxytrex, uses an ULD opioid antagonist to minimize physical dependence following chronic opioid use.

"These data are robust," said Nadav Friedmann, PhD, MD, Pain Therapeutics' chief medical and operating officer. "We believe these findings strengthen the rationale for the clinical development of Oxytrex, as they clearly demonstrate a novel and powerful mechanism of action."

Technical Publications

The new publication is titled, "G[beta][gamma] That Interacts with Adenylyl Cyclase in Opioid Tolerance Originates from a Gs Protein" (Wang and Burns, 2006, Journal of Neurobiology 66:1302-1310). Today's poster presentation at the 36th Annual Meeting of the Society for Neuroscience is titled, "Ultra-low-dose Naloxone Reduces Mu Opioid Receptor Excitatory Signaling in Rat Striatal Slice Organotypic Cultures" (Wang, Burns, Shen, Bakshi). Collectively, these data build on a 2005 publication in Neuroscience by the same lead researcher demonstrating that tolerance, dependence and opioid excitatory signaling are all prevented by co-treatment with an ULD opioid antagonist (Wang et al, 2005, Neuroscience 135:247-261). All three publications are available on Pain Therapeutics' web site,

About Oxytrex

Oxytrex is a novel, next-generation painkiller being developed exclusively by Pain Therapeutics for the treatment of severe chronic pain. The Company believes Oxytrex provides strong pain relief and less physical dependence than currently marketed opioid painkillers. Oxytrex combines an ultra-low-dose opioid antagonist, such as naltrexone, with an opioid agonist, such as oxycodone. The Company believes it remains on-track to announce in Q4 2006 the initiation of a Phase III trial using ULD opioid antagonist in patients with severe chronic pain.

About Pain Therapeutics, Inc.

Pain Therapeutics is a biopharmaceutical company that develops novel drugs. We have three investigational drug candidates in clinical programs. Remoxy(TM) and PTI-202 are proprietary, abuse-resistant forms of opioid drugs. Oxytrex is a novel, next-generation painkiller that potentially offers less physical dependence than currently marketed opioid painkillers. These three drugs target different segments of the multi-billion dollar market to treat severe chronic pain, such as persistent low-back pain or pain due to advanced stages of osteoarthritis. The FDA has not yet evaluated the merits, safety or efficacy of our drug candidates.

Note Regarding Forward-Looking Statements: This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the "Act"). Pain Therapeutics disclaims any intent or obligation to update these forward-looking statements, and claims the protection of the Safe Harbor for forward-looking statements contained in the Act. Examples of such statements include, but are not limited to, any statements relating to the timing, scope or expected outcome of the Company's clinical development of Oxytrex or its regulatory approval, the potential benefits of Oxytrex and the Company's drug candidates and the size of the potential market for the Company's products, including Oxytrex. Such statements are based on management's current expectations, but actual results may differ materially due to various factors. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to difficulties or delays in development, testing, regulatory approval, production and marketing of the Company's drug candidates, unexpected adverse side effects or inadequate therapeutic efficacy of the Company's drug candidates that could slow or prevent product approval or market acceptance (including the risk that current and past results of clinical trials are not necessarily indicative of future results of clinical trials), the uncertainty of patent protection for the Company's intellectual property or trade secrets, the Company's ability to obtain additional financing if necessary and unanticipated research and development and other costs. For further information regarding these and other risks related to Pain Therapeutics' business, investors should consult the Company's filings with the Securities and Exchange Commission.

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