UNC scientists and collaborators have made progress toward their goal of developing opioid medications without negative side effects among a growing opioid epidemic in North Carolina and the United States.
One of the lead researchers is Dr. Daniel Wacker, who said the focus of the research is to understand how specific drugs interact with receptors in the body that give the effects of that drug.
“So our focus really was to understand how they interact in a molecular or atomic detail fashion with the receptor and then make suggestions to chemists how to improve them, how to build drugs that are safer, how to build drugs that are potentially more efficacious,” said Wacker.
UNC scientists were able to use a technology called X-ray crystallography to create a 3-D, high resolution image of an opioid receptor bound to an opioid.
“It’s helped us identify which interactions between the chemical and the receptor were important for pain reliving effects, which one of these interactions were involved in the side effects of these compounds,” Wacker said. “So with that blue print enhanced, the goal is, of course, to go to a chemist and say, ‘Hey, can you build upon these interactions that are really important and take away the other ones that are most likely causing side effects.'”
UNC scientists and collaborating chemists have already created the first compound without certain side effects. Wacker says one of the negative side effects the scientists looked to remove is an activation of the limbic system in the brain, which causes a rewarding effect and is what can lead to addiction.
The other main side effect that Wacker and his team worked to remove, which Wacker said is responsible for opioid overdoses and deaths, is respiratory depression or suffocation. Other side effects eliminated were hallucinations and dysphoric effects.
Wacker said under the current progressions, researchers were “almost months out” from knowing the next effective steps.
“In the study, we’ve presented a blue print on how to design a novel compound. We’ve already made one of those, and we’re now carefully putting them into animal models, mice mainly, to see what the effects really are. And we’re really optimistic that that opens an entirely new avenue of drug,” said Wacker.
Wacker says he’s happy to see the work, published in the journal Cell, being validated with most of the compounds panning out, as well as all the focus on the opioid epidemic, which he calls an exponentially growing problem.
North Carolina alone saw a 73 percent increase in opiate-related deaths between 2005 and 2015, according to the North Carolina Department of Health and Human Services. Wilmington is the top city in the nation for opioid abuse, with more than 11.6 percent of the population abusing opiates. Hickory, Jacksonville and Fayetteville were also in the top 25 cities in the US with high opioid abuse.
In efforts to combat the epidemic, Governor Roy Cooper signed the Strengthen Opioid Misuse Prevent or (STOP) Act into effect beginning January 1, 2018, which places stricter limits on how many opioids doctors can prescribe to first-time patients suffering from pain.
Wacker says the next step for the research is to involve people who understand patient treatment to go from a mechanistic study to a clinical study.
Photo via Blake Hodge
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