Research RoundUp: In search of safer opioids

The Research Roundup has expanded to provide a more in-depth insight into publications from across the Faculty. MIPS is releasing weekly summaries highlighting a selection of papers from each theme. If you have a recent publication that you would like to see featured, please email us and we'll pop it in the next edition.

Opioids, such as morphine, are the most effective analgesics that currently exist but they also cause serious side effects, including addiction and respiratory depression – the main cause of death by overdose. The increased dependence on opioids for the control of pain, and their severe side effects, has led to a global “opioid crisis”. In Australia, opioid overdose deaths increased by 20% over the last five years and now represent 50% of all drug-related deaths.


Amidst this global opioid epidemic, researchers around the world have been trying to develop safer opioid analgesics. Opioids work by activating a receptor protein on the surface of cells. This receptor can then stimulate either “good” or “bad” pathways in the cell which result in pain relief or respiratory depression, respectively.

This knowledge allowed researchers to develop a new generation of opioid drugs, called “biased opioids”; so-called because it was thought that they could bias the receptor protein to only activate pain relief pathways. The new generation opioids can still cause pain relief but were reported to have fewer side effects.

In this publication, researchers, Michelle Halls and Arisbel Gondin from the Drug Discovery Biology Theme demonstrate that these new generation opioids are not actually biased towards pain relief. The new opioids can still activate pathways leading to respiratory depression. However, the new opioids seem to cause weaker activation of all pathways (both good and bad) than most classical opioids. This weaker activation of all pathways is ultimately good, as it generates a larger therapeutic window. Meaning that the new generation opioids can still provide sufficient pain relief without dose-limiting side effects. This is critical information, as some of these new drugs are currently seeking approval by the FDA. It will also help to direct the search for better opioid drugs in the future.

Article: Low intrinsic efficacy for G protein activation can explain the improved side effect profiles of new opioid agonists

MIPS authors: Arisbel Gondin, Michelle Halls & Meritxell Canals

Access the article here