Scientists Building a Safer Opioid

By Pat Anson, Editor

Researchers at the University of North Carolina believe they’ve found a way to create a new type of opioid medication that relieves pain without risky side effects.

Currently, opioid painkillers bind to several opioid receptors on the surface of brain cells, triggering a wide range of side effects -- from nausea, numbness and constipation to anxiety, addiction and potentially fatal respiratory depression.

The UNC researchers report in the journal Cell that they have created a new drug compound that only activates the kappa opioid receptor – the brain receptor that is the key to pain relief.

"To create better opioids, we need to know the structure of their receptors," said senior author Bryan Roth, MD, a professor in the Department of Pharmacology at UNC School of Medicine.

"Until recently, this was impossible. But now we know the structure of the activated kappa opioid receptor. And we showed we can actually use the structure to make a drug-like compound with better properties than current opioids."

The compound was created in cell cultures in Roth's lab, and still needs to be tested in animal models. But knowing the detailed structure of the kappa opioid receptor (KOR) has opened the door to developing other drug-like compounds that are highly selective for specific opioid receptors.

KAPPA OPIOID RECEPTOR (unc IMAGE)

"Tens of thousands people who take opioids die every year, and so we need safer and more effective drugs for treating pain and related conditions," Roth said in a news release. "One of the big ideas is to target KORs because the few drugs that bind to it don't lead to addiction or cause death due to overdose. Those side effects are mainly related to actions at the mu opioid receptor."

Drugs that bind to KORs can still have side effects, such as hallucinations and dysphoria - a state of unease or dissatisfaction with life related to anxiety and depression. That is why scientists say it’s important to know how this receptor is activated – so they can figure out a way to bind a compound to KORs so that it only relieves pain.

"Now we have a much better understanding of the direction we have to explore in order to create a selective drug to activate only kappa opioid receptors," said corresponding author Daniel Wacker, PhD, UNC School of Medicine.

The UNC research was funded by the National Institutes of Health, the Mayday Fund, and the Peter F. McManus Trust.