Experimental Drug Molecule May Prevent Opioid Misuse

Novel investigational compound observed to treat chronic pain without side effects.

Investigators have created a novel way to develop painkillers that reduce pain in inflamed tissues, but bypasses serious side effects typically associated with the drugs.

In a study published in Science, the authors used a computer simulation to evaluate interactions at the opioid receptors, which are targeted by painkillers. In animal models, the study authors found that the morphine-like compound was able to reduce pain, and prevent harm to healthy tissues.

Opioids are typically used to treat pain linked to tissue damage and inflammation, such as from surgery, nerve damage, arthritis, or cancer. While these drugs can offer benefits to some patients, they are also known to cause drowsiness, nausea, constipation, dependency, and respiratory arrest.

Although many patients are prescribed opioids, studies have found these drugs to be ineffective in treating many pain-related conditions, including back pain. The American College of Physicians recently updated guidelines to recommend that patients and physicians treat acute or subacute low back pain without drug therapy.

Alternative therapies, such as heat, massage, acupuncture, or spinal manipulation should be the first line of treatment for patients with acute or subacute pain. Opioids are not included in the recommendations to treat back pain at all.

The drugs have also been at the center of an epidemic, with many individuals dying from an overdose related to opioid misuse disorder.

In the study, the researchers used computational simulations to analyze morphine-like molecules and their interactions with opioid receptors.

“By analyzing drug-opioid receptor interactions in damaged tissues, as opposed to healthy tissues, we were hoping to provide useful information for the design of new painkillers without harmful side effects,” said researcher Dr Christoph Stein.

The authors were then able to discover a mechanism of action that can target pain, according to the study. The investigators believe that treating postoperative and chronic inflammatory pain without side effects may be a possibility, and could improve quality of life for patients.

This prototype could play a significant role in creating novel drugs that deter abuse, and do not cause other serious side effects.

“In contrast to conventional opioids, our NFEPP-prototype appears to only bind to, and activate, opioid receptors in an acidic environment,” the authors wrote. “This means it produces pain relief only in injured tissues, and without causing respiratory depression, drowsiness, the risk of dependency, or constipation."

After creating a prototype, investigators conducted experimental tests. Through computer modeling, the authors simulated the acidic conditions of inflamed tissues by increasing proton concentrations.

“We were able to show that the protonation of drugs is a key requirement for the activation of opioid receptors,” the authors wrote.

These findings may apply to pain caused by other factors, and could be used for further studies of drug receptors. The authors believe that the benefits of increased efficacy and tolerability could translate to other classifications of drugs besides painkillers, the study concluded.