Virus - Respiratory Infections

Scientists on the Florida campus of The Scripps Research Institute (TSRI) in America have developed new opioid pain relievers that reduce pain on a par with morphine but do not slow or stop breathing, the cause of opiate overdose.

The research outlines a method for making safer opioid painkillers, which is important because, according to the U.S. Centers for Disease Control and Prevention, 91 Americans die every day from opioid overdoses. The deaths are caused when opiates like oxycontin, heroin and fentanyl slow and eventually stop a person’s breathing.

Study leader TSRI Professor Laura M. Bohn, Ph.D., said the research shows that a range of compounds can block pain without affecting respiration.

The study builds on two decades of research by Prof Bohn and her colleagues, who have questioned whether the painkilling pathway, called the G protein pathway, could be separated from the breathing suppression pathway, called the beta-arrestin pathway.

Prof Bohn said: “One of the questions we had was how good we can get at separating out the pathways, and how much separation do we need to see analgesia without respiratory suppression.”

For the study, she worked closely with TSRI chemist Thomas Bannister, Ph.D, to develop new potential drug molecules; they then adapted their chemical structures to systematically vary the ‘bias’ between the two pathways—G protein signaling and beta-arrestin recruitment.

The group have developed more than 500 compounds in the past six years and found more than 60 that showed bias between signalling assays. They selected six compounds to represent a wide range in the degree of bias from those that preferred barrestin2 recruitment to those that almost exclusively preferred G protein signalling.

The researchers found that the new compounds could enter the brain and all of the compounds were as potent, if not more so, than morphine.

Prof Bohn said: “I think what we have done here is shown that bias isn’t all or none—that there is a spectrum.”

The findings suggest an opportunity to expand the range of doses at which a drug may be administered safely, she said.

The results today are the culmination of work by TSRI scientists including Cullen Schmid, Ph.D., Nicole Kennedy, Ph.D., and Michael Cameron, Ph.D., as well as former members of the research lab: Jenny Morgenweck, Ph.D., Zhizhou Yue, Ph.D., Kim Lovell, Ph.D. and Nicolette Ross, Ph.D. The work was funded by the National Institute on Drug Abuse of the National Institutes of Health.