Chemical compound shows promise as alternative to opioid pain relievers

July 15, 2013

A drug targeting a protein complex containing two different types of opioid receptors may be an effective alternative to morphine and other opioid pain medications, without any of the side effects or risk of dependence, according to research led by the Icahn School of Medicine at Mount Sinai. The findings are published in July in the journal Proceedings of the National Academy of Sciences.

Morphine is still the most widely-used , or analgesic, in people with severe pain, but chronic use can lead to addiction and negative side effects such as respiratory issues, constipation, or diarrhea.

In a previous study published in Science Signaling by Lakshmi Devi, PhD, Professor of Pharmacology and Systems Therapeutics at Mount Sinai, researchers identified a called a GPCR heteromer, which is a protein complex that is made up of two called mu and delta. They also showed that the heteromer is abundant in the area of the brain that processes pain, and is the likely cause of morphine tolerance and side effects.

In the current study, Dr. Devi carried out high throughput screening in collaboration with researchers at the National Institutes of Health (NIH) to identify which small molecules might act on the signaling pathway associated with this protein complex. Researchers found one compound called CYM51010 that was as potent as , but less likely to result in tolerance and negative side effects. Dr. Devi's team is currently developing modified versions of this compound that may have potential as analgesics with reduced side effects.

"GPCR heteromers have been suggested to represent powerful targets for improved, novel therapeutics with reduced adverse effects in people with ," said Dr. Devi. "However, there are presently no chemical tools that allow us to investigate their role in vivo. Our work represents a promising step in this direction, providing results that pave the way towards a new understanding of the function and pharmacology of opioid receptor heteromers."

Dr. Devi and her team are currently working with co-author Marta Filizola, PhD, Associate Professor of Structural and Chemical Biology at Mount Sinai, to learn how CYM51010 binds to the protein complex. Armed with this information, they hope to modify the compound to treat pain without the development of dependency. They also plan to restrict their benefit to the gastrointestinal system and treat diarrhea associated with irritable bowel disease that is unresponsive to existing therapies.

Explore further: Reformulated imatinib eliminates morphine tolerance in lab studies

More information: Identification of a ?-? opioid receptor heteromer-biased agonist with antinociceptive activity, PNAS, Published online before print July 1, 2013, doi: 10.1073/pnas.1222044110

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not rated yet Jul 16, 2013
ANY analgesic has a risk of dependence. It is not the substance that is habit forming, but the relief from pain that addicts crave.
not rated yet Jul 25, 2013
Have to disagree with you tadchem. Opiates are infinitely more addictive than for example NSAIDS, and this is attributed to the lack of euphoria/pleasure/causing a 'high' that opiates produce. A painkiller that doesn't cause a 'high' could still be abused, but not as a means to get high which is how most opiates are abused.

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