Scripps Florida scientists have been awarded $3.1 million by the National Institute on Drug Abuse, part of the National Institutes of Health, to study and develop several new compounds that could prove to be effective in controlling pain without the unwanted side effects common with opiate drugs, such as morphine, Oxycontin®, and Vicoden®.
Laura Bohn, an associate professor in the Department of Molecular Therapeutics and Neuroscience at Scripps Research, and Thomas Bannister, an assistant professor in the Department of Chemistry and associate scientific director in the Translational Research Institute at Scripps Research, will serve as joint principal investigators for the new five-year study.
Their study will focus on four new classes of compounds that appear to differ fundamentally from opiates in the side effects that they can produce.
“Once we more fully understand how these compounds work, we expect to optimize and develop them as novel drugs,” said Bohn. “We hope to produce potent pain relievers without the problems associated with current treatments.”
The adverse side effects of morphine and other opiate drugs can range from the uncomfortable (constipation) to the dangerous (addiction, respiratory suppression, and death by overdose).
While the new compounds bind and activate the same receptor as morphine—the mu opioid receptor or MOR—they do so in a way that avoids recruiting the protein beta arrestin 2. Genetic studies have shown that animal models lacking beta-arrestins experience robust pain relief with diminished side effects.
In an encouraging sign for further development, compounds in the four chemical classes have already been synthesized by Bannister’s medicinal chemistry group.
“We designed compounds intended to have biological activity in the brain,” said Bannister. “While we expected to find pain relievers, we were thrilled to see that some compounds also had the chemical and biological properties necessary for showing reduced side effects. The added financial support should help us build upon these exciting results and identify safer pain medications.”