New painkillers without dangerous side effects

Serious side effects with pain medication in the future avoidable?
At the Charité - Universitätsmedizin Berlin, physicians have developed a new pain medication, which has a similar effect as painkillers based on opioids, but without corresponding side effects. The discovery of the new mechanism of action called the researchers as a breakthrough in pain medication.

The scientists of the Charité have found a new way to develop pain medication. The researchers used computer simulations to analyze the interactions of different molecules with opioid receptors. These are the docking points for most pain medications. The results of their research published in the journal "Science".

Scientists have discovered a new mechanism of action for analgesics that minimizes the risk of unwanted side effects. (Image: ra2 studio / fotolia.com)

Conventional painkillers with serious side effects
Opioids are used in many common painkillers. They have a strong analgesic effect and are used "especially for pain caused by tissue injury and inflammation, for example after surgery, nerve injuries, arthritis or tumor diseases", the scientists report. However, the drugs often show serious side effects. These include, according to the researchers, for example, "drowsiness, nausea, constipation and addiction, in some cases even respiratory arrest." The Berlin researchers therefore looked for alternatives for the pain medication. For this they used the method of computer simulation.

Computer simulation for the analysis of possible drugs
"We hypothesized that analyzing the interactions between drugs and opioid receptors in injured tissue, as opposed to healthy tissue, could be used to design new pain relievers without harmful side effects," explains Professor Dr. Christoph Stein, Director of the Charité Clinic for Anaesthesiology. Through innovative computer simulation in collaboration with Privatdozent Dr. med. Marcus Weber from the Zuse Institute Berlin, the researchers were able to analyze morphine-like molecules and their interaction with opioid receptors.

New mechanism of action identified
With the help of the computer models, the scientists were able to identify a "new mechanism of action that achieves pain relief exclusively in inflamed tissue, ie the desired target site," reports the Berlin Charité. Postoperative pain and chronic inflammatory pain can be treated in this way without side effects and the quality of life of patients can be significantly improved. "In contrast to conventional opioids, our prototype NFEPP shows binding and activation of opioid receptors only in an acidic environment and thus inhibits pain only in injured tissue, without causing respiratory depression, drowsiness, addiction or constipation", emphasize the study's first authors. Viola Spahn and dr. Giovanna Del Vecchio.

Active ingredient extremely successful in the test
The scientists designed, synthesized and subsequently tested the active substance prototype NFEPP. In computer models, among other things, an increased proton concentration, ie an acidification as in the case of an inflammation, was simulated. "It has been shown that the protonation of drugs is a crucial prerequisite for the activation of opioid receptors," the scientists report. In the animal model, the prototype of a morphine-like molecule actually achieved severe analgesia in inflamed tissue, while healthy tissue did not respond to the drug. Serious side effects, such as those that occur with opioids, are thus preventable. (Fp)