4a,9-dihydroxy-7a-(hydroxymethyl)-3-methyl-2,3,4,4a,5,6-hexahydro-1H-4,12-methanol benzofuro[3,2-e]isoquinoline-7(7aH)-one (UMB 425)
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."
