A promising new non-opioid painkiller (analgesic) with possibly less adverse effects than previous powerful painkillers has been developed.

A team of scientists from the University of Warwick’s School of Life Sciences examined BnOCPA (benzyloxy-cyclopentyladenosine), which was revealed to be a potent and selective analgesic that is non-addictive in test model systems. BnOCPA also possesses a distinct mechanism of action, which might pave the way for the development of novel analgesic medicines.

The study, which was done by the University of Warwick in partnership with academics from the University of Bern, the University of Cambridge, Coventry University, Monash University, and industry groups, was just published in the journal Nature Communications.

In the United Kingdom, one-third to half of the population reports having chronic pain that is moderately or severely debilitating. Such discomfort has a significant impact on one’s quality of life, and many of the commonly prescribed medications have adverse effects. Opioids, such as morphine and oxycodone, are addictive and hazardous when taken excessively. As a result, there is an unmet need for novel, potent painkillers.

Many drugs function by activating adapter molecules on the cell surface known as G proteins. G protein activation can result in a range of biological consequences. Because BnOCPA activates just one kind of G protein, its activities are exceedingly selective, reducing the risk of unwanted side effects.

“The selectivity and strength of BnOCPA make it genuinely unique,” said Dr. Mark Wall of the University of Warwick’s School of Life Sciences, who led the research. “We think that with additional research, it will be able to develop strong painkillers to assist patients manage with chronic pain.”

Professor Bruno Frenguelli of the University of Warwick’s School of Life Sciences, the project’s primary investigator, remarked, “This is a beautiful example of serendipity in science.” We had no expectations that BnOCPA would act differently from other molecules in its class, but the more we looked into it, the more traits we uncovered that had never been observed before, potentially opening up new fields of medicinal chemistry.”

“This is an excellent narrative looking at agonist bias for a GPCR,” stated Professor Graham Ladds, co-principal investigator on the research at the University of Cambridge. BnOCPA not only has the potential to be a novel type of painkiller, but it has also demonstrated a new strategy for targeting additional GPCRs in drug development.”