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A Path to Lower-Risk Painkillers

New drug target paves way for alternatives to morphine (June 10)

For patients managing cancer and other chronic health issues, painkillers such as morphine and hydrocodone are often essential for pain relief. The body’s natural tendency to develop tolerance to these medications, however, often requires patients to take higher doses — increasing risks of harmful side effects and dependency.

New research from the University of Michigan Health System has identified a novel approach to moderate and severe pain therapy that paves the way for lower-dosage painkillers. The findings were published in the Proceedings of the National Academy of Sciences of the United States of America.

Drugs such as hydrocodone (the main ingredient of Vicodin; AbbVie) and oxycodone (OxyContin; Purdue Pharma) are often the best options for the treatment of moderate-to-severe pain for patients with medical conditions ranging from a wisdom tooth extraction to cancer. The drugs bind to specific molecules (opioid receptors) on nerve cells in the brain and spinal cord to prevent the feeling of pain.

“We have for the first time discovered compounds that bind to an alternative site on the nerve opioid receptors and that have significant potential to enhance the drug’s positive impact without increasing negative side effects,” says co-author John Traynor, PhD.

“We are still in the very early stages of this research with a long way to go, but we believe identifying these compounds is a key step in revolutionizing the treatment of pain. This opens the door to developing pain relief medications that require lower doses to be effective, helping address the serious issues of tolerance and dependence that we see with conventional pain therapy.”

Using cell systems and mouse brain membranes, researchers have identified compounds that bind to a physically distinct and previously unknown site on the opioid receptor — a site that fine-tunes the activity of the receptor. Not only do these compounds act at a location that hasn’t been studied as a drug target before, but they bind to the receptor in a new way to enhance the actions of morphine — which means lower doses can have the same effect.

“The newly discovered compounds bind to the same receptor as morphine but appear to act at a separate novel site on the receptor and therefore can produce different effects. What’s particularly exciting is that these compounds could potentially work with the body’s own natural painkillers to manage pain,” Traynor says.

Source: University of Michigan; June 10, 2013.

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