A new way of developing painkillers has been discovered by researchers from Charité – Universitätsmedizin Berlin. A team of scientists used computational simulation to analyze interactions at the cell’s docking sites for painkillers. These sites are called the opioid receptors. When their prototype of a morphine-like molecule was used in an animal model, it was able to produce substantial pain relief in inflamed tissues while healthy tissues remained unaffected. This suggests that the severe side effects currently associated with these types of painkillers could be avoided.

Opioids are a type of strong painkillers that are mostly used to treat pain associated with inflammation and tissue damage, such as that caused by arthritis, nerve damage, surgery, or cancer. They do exhibit common side effects including nausea, drowsiness, dependency and constipation, and, in some cases, respiratory failure.

Prof. Dr. Christoph Stein, Head of the Department of Anesthesiology and Surgical Critical Care Medicine on Campus Benjamin Franklin, cooperated with PD Dr. Marcus Weber from the Zuse Institute Berlin for the study. Stein explained that they were hoping to provide useful information for the design of new painkillers without harmful side effects by analyzing drug opioid receptor interactions in damaged tissues, as opposed to healthy tissues.

Using innovative computational simulations, the team was able to scrutinize morphine-like molecules and their interactions with opioid receptors. They were able to detect a new mechanism of action successfully. This mechanism is able to produce pain relief in the desired target tissues affected by inflammation only.

Dr. Giovanna Del Vecchio and Dr. Viola Spahn, the study’s first authors explained that treating chronic inflammatory and postoperative pain should now be possible without causing side effects, thus improving patient quality of life substantially. Unlike conventional opioids, the NFEPP-prototype only binds to and activates opioid receptors in acidic environments, producing pain relief only in injured tissues. This also eliminates respiratory depression, drowsiness, the risk of dependency and constipation.

The team subjected the drug prototype to experimental testing after designing and synthesizing it. They then simulated an increased concentration of protons using computer modeling. This mimicked the acidic conditions found in inflamed tissues. The authors concluded by saying that they were able to show that the protonation of drugs is a key requirement for the activation of opioid receptors. Their findings may also apply to other types of pain and could even find application in other areas of receptor research. The benefits of improved drug efficacy and tolerability are therefore not limited to only painkillers, but may well include other drugs as well.

This research has been published in the journal Science.