Researchers develop new opioid drug for chronic pain

A team of researchers led by Andrew Coop, PhD, professor and chair of the Department of Pharmaceutical Sciences (PSC) at the University of Maryland School of Pharmacy (UMSOP), has developed a new opioid drug that shows great potential to advance treatment and improve quality of life for individuals living with chronic pain. Spotlighted in a recent issue of ACS Chemical Neuroscience, the compound, known as UMB 425, is as strong as morphine, but displays diminished tolerance over time with no obvious toxic effects.

"UMB 425 is a breakthrough in the development of therapeutics to treat chronic pain," says Coop. "Unlike other drugs developed to act on only one biological target, UMB 425 acts on two different opioid receptors in the body. When activated at the same time, these receptors work together to provide pain relief and slow the body's development of tolerance to the drug. This diminished tolerance allows a lower dose of the opioid to be administered for a longer time period, while still achieving the same level of pain relief."

For individuals living with chronic pain, either as a result of injury or disease such as arthritis, opioids are the standard treatment. But as the dosage increases to offset the body's tolerance to their effects, opioids cause a number of adverse effects, including constipation, nausea, drowsiness, and dizziness. The unique dual-profile of UMB 425 - made possible through Coop's collaborations with Alexander MacKerell, PhD, professor in PSC and director of the School's Computer Aided Drug Design Center, and Maureen Kane, PhD, assistant professor in PSC and co-director of the School's Mass Spectrometry Facility - provides both pain relief as well as diminished tolerance in one drug.

"Historically, medicinal chemists have developed drugs aimed at only one biological target," says Coop. "However, two drugs administered together have the potential to metabolize differently in different individuals, as well as affect patients' adherence to both drugs. A single compound that is able to provide both pain relief and diminished tolerance has the advantage of a defined ratio that we can optimize to ensure patients receive the maximum pain relief, while experiencing minimum adverse effects."

Coop and his team conducted several in vitro and in vivo studies to determine the drug's effectiveness in alleviating pain and diminishing tolerance over time. If future research and clinical trials are successful, UMB 425 could have a significant impact on the treatment and quality of life for individuals living with chronic pain.

"The clinical implication of this research has the potential to be tremendous," says Mary Lynn McPherson, PharmD, BCPS, CPE, professor and vice chair for academic affairs in the Department of Pharmacy Practice and Science, and an international authority in the fields of pain management and palliative care. "If clinicians can prescribe lower doses of opioids, they will not have to raise a patient's dose because of tolerance to the analgesic effects. Using lower doses will result in less severe adverse effects for the patient, both short-term effects such as nausea and constipation, as well as long-term adverse effects on the endocrine and immunologic systems. This would be a highly significant advance in pain management."

Coop and his team will continue to test UMB 425 to determine an optimal ratio at which it acts on the targeted opioid receptors to maximize pain relief, while minimizing tolerance. The team's ultimate goal is to develop two compounds derived from UMB 425 that will lead to Phase I clinical trials.