A promising new non-opioid pain reliever (analgesic) has been discovered, with potentially fewer side effects than other powerful pain relievers.
A team of researchers led by scientists from the University of Warwick’s School of Life Sciences analyzed a compound known as BnOCPA (benzyloxy-cyclopentyladenosine), which was found to be a potent and selective non-addictive analgesic in test model systems. BnOCPA also has a unique mode of action, which could provide a new pathway for the development of analgesic drugs. The study, conducted by the Warwick team in collaboration with researchers from the University of Bern, University of Cambridge, Coventry University, Monash University and industry organisations, was recently published in the journal Nature Communications. In the UK, between a third and a half of the population report having chronic pain that causes either moderate or severe disability. This pain negatively affects quality of life, and many of the commonly prescribed pain medications have side effects. Opioids, such as morphine and oxycodone, can be addictive and dangerous when taken in excess. There is therefore an unmet need for new, potent painkillers. Many drugs work by activating adapter molecules known as G proteins on the cell surface. Activation of G proteins can cause a variety of cellular effects. Because only one type of G protein is activated by BnOCPA, its actions are highly selective, minimizing the potential for negative side effects. Dr Mark Wall, from the School of Life Sciences at the University of Warwick, who led the research, said: “The selectivity and potency of BnOCPA make it truly unique and we hope that with further research it will be possible to produce powerful painkillers that can help patients to deal with chronic pain.” Professor Bruno Frenguelli, the project’s principal investigator, from the University of Warwick’s School of Life Sciences, added: “This is a fantastic example of peace in science. We did not expect that BnOCPA would behave differently from other molecules in its class, but the more we looked at BnOCPA we discovered properties that had not been seen before and that may open up new areas of medicinal chemistry.” Professor Graham Ladds, co-principal investigator of the project, from the University of Cambridge, said: “This is an amazing story looking at the agonist bias of a GPCR. Not only does BnOCPA have the potential to be a new type of pain reliever, but it has shown us a new method for targeting other GPCRs in drug discovery.” Reference: “Selective activation of Gaob by an A1 adenosine receptor agonist induces analgesia without cardiorespiratory depression” by Mark J. Wall, Emily Hill, Robert Huckstepp, Kerry Barkan, Giuseppe Deganutti, Michele Leuenberger, Barbara Preti, Ian Winfield Sabr, Suchankova, Haifeng Wei, Dewi Safitri, Xianglin Huang, Wendy Imlach, Circe La Mache, Eve Dean, Cherise Hume, Stephanie Hayward, Jess Oliver, Fei-Yue Zhao, David Spanswick, Christopher A. Reynolds, Martin Lochner, and Graham Lad Bruno G. Frenguelli, 18 July 2022, Nature Communications.DOI: 10.1038/s41467-022-31652-2
