Chemical Compound Shows Promise as Alternative to Opioid Pain Relievers
Drug targeting a protein complex containing two different types of opioid receptors may be an effective alternative to morphine and other opioid pain medications.
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 pain reliever, 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 therapeutic target called a GPCR heteromer, which is a protein complex that is made up of two opioid receptors 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 morphine, 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 severe pain,” 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.
This study was supported by National Institute on Drug Abuse Grants R01-008863 and K05-019521.
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai. Established in 1968, the Icahn School of Medicine at Mount Sinai is one of the leading medical schools in the United States. The Icahn School of Medicine is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty members in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by U.S. News & World Report.
The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation’s oldest, largest and most-respected voluntary hospitals. In 2012, U.S. News & World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation’s top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of just 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and by U.S. News & World Report and whose hospital is on the U.S. News & World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.
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About the Mount Sinai Health System
Mount Sinai Health System is one of the nation’s leading integrated academic health systems and one of the largest in the New York metropolitan area. Its comprehensive system includes seven hospitals, more than 400 outpatient practices, over 600 research and clinical laboratories, the Icahn School of Medicine at Mount Sinai, the Graduate School of Biomedical Sciences, and the Mount Sinai Phillips School of Nursing. Together, the Health System comprises approximately 48,000 employees, more than 9,000 physicians, and 8,600 nurses.
As a leading learning health system, Mount Sinai combines clinical expertise with scientific discovery to improve patient care while training the next generation of health care and biomedical leaders. The Health System provides care across every stage of life, from prenatal care through geriatrics, while advancing personalized medicine through artificial intelligence, data science, and biomedical research.
Mount Sinai is consistently recognized among the nation’s leading academic health systems for patient care, research, and education. The Mount Sinai Hospital is ranked No. 1 in New York by Newsweek and No. 5 on the magazine’s World’s Best Hospitals list. The Icahn School of Medicine at Mount Sinai ranks No. 11 among U.S. medical schools and No. 1 among freestanding medical schools for National Institutes of Health funding, reflecting the strength of its scientific enterprise and leadership in biomedical research.