by Stephanie Rees
Opioid analgesics, such as morphine and oxycodone, are commended for their strong pain-relieving properties and are currently the most powerful class of painkillers available. However, associated with the use of opioids are a series of unpleasant and dangerous side effects ranging from constipation and drowsiness to respiratory depression – the most common cause of death in acute opioid poisoning.
Opioid analgesics exert their action by binding to opioid receptors which are widely distributed throughout the brain, as well as in the spinal cord and GI tract. Due to a lack of specificity of these drugs for opioid receptors only where tissue damage exists, the side effect profile is quite frankly scary.
Researchers at a teaching hospital in Berlin, Charité — Universitätsmedizin Berlin, believe they may have discovered a way to counteract the extensive side effect profile of opioids by identifying a new mechanism of action which produces pain relief only in injured tissues and thus avoids unnecessary production of side effects.
With the aid of computational simulations, the researchers analysed the interactions between morphine-like molecules and opioid receptors. The findings showed their prototype – NFEPP, to only bind to and activate opioid receptors in an acidic environment (mimicking the acidic conditions observed in inflamed tissues), whilst non-acidic areas remained unaffected by the drug, suggesting the feasibility of selectively bypassing healthy tissues to act only at injured tissues. The prototype then underwent testing in rat models experiencing inflammatory pain; it was shown to exert pain-relieving action without the standard presence of side effects. The study’s first authors, Dr. Viola Spahn and Dr. Giovanna Del Vecchio, explained, “This means it produces pain relief only in injured tissues, and without causing respiratory depression, drowsiness, the risk of dependency, or constipation.”.
Further testing is required, but if successful this new mechanism would significantly improve the quality of life for patients, as well as paving the way for other drug discoveries via similar mechanisms.