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: A path to lower-risk painkillers

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

Related Stories

A path to lower-risk painkillers

June 10, 2013
For patients managing cancer and other chronic health issues, painkillers such as morphine and Vicodin are often essential for pain relief. The body's natural tendency to develop tolerance to these medications, however, often ...

Missing enzyme linked to drug addiction

June 17, 2013
A missing brain enzyme increases concentrations of a protein related to pain-killer addiction, according to an animal study. The results will be presented Monday at The Endocrine Society's 95th Annual Meeting in San Francisco.

Reformulated imatinib eliminates morphine tolerance in lab studies

February 21, 2012
By reformulating the common cancer drug imatinib (Gleevec), researchers have eliminated morphine tolerance in rats – an important step toward improving the effectiveness of chronic pain management in patients, according ...

A new promising approach in the therapy of pain

December 4, 2012
The treatment of inflammatory pain can be improved by endogenous opioid peptides acting directly in injured tissue. Scientists at the Charité – Universitätsmedizin Berlin and the Université Paris Descartes showed that ...

Recommended for you

Research redefines proteins' role in the development of spinal sensory cells

September 19, 2017
A recent study led by Samantha Butler at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA has overturned a common belief about how a certain class of proteins in the spinal cord regulate ...

The brain at work: Spotting half-hidden objects

September 19, 2017
How does a driver's brain realize that a stop sign is behind a bush when only a red edge is showing? Or how can a monkey suspect that the yellow sliver in the leaves is a round piece of fruit?

Team discovers how to train damaging inflammatory cells to promote repair after stroke

September 19, 2017
White blood cells called neutrophils are like soldiers in your body that form in the bone marrow and at the first sign of microbial attack, head for the site of injury just as fast as they can to neutralize invading bacteria ...

Epileptic seizures show long-distance effects

September 19, 2017
The area in which an epileptic seizure starts in the brain, may be small but it reaches other parts of the brain at distances of over ten centimeters. That distant activity, in turn, influences the epileptic core, according ...

Study uncovers markers for severe form of multiple sclerosis

September 18, 2017
Scientists have uncovered two closely related cytokines—molecules involved in cell communication and movement—that may explain why some people develop progressive multiple sclerosis (MS), the most severe form of the disease. ...

Genetically altered mice bear some hallmarks of human bipolar behavior

September 18, 2017
Johns Hopkins researchers report they have genetically engineered mice that display many of the behavioral hallmarks of human bipolar disorder, and that the abnormal behaviors the rodents show can be reversed using well-established ...

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

tadchem
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.
captainkolak
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.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.