The Scripps Research Institute in Florida, US, which published a study in biology journal Cell last week, told us that its recently-discovered compounds were at least as potent as morphine, and less likely to induce respiratory suppression in mouse models.
The researchers tweaked the chemical structures of the potential molecules to vary the ‘bias’ between the two pathways, which the Institute’s Laura Bohn described as G protein signalling and beta-arrestin recruitment.
“Biased agonism refers to the ability of a drug to refine receptor signalling toward or away from engaging with signalling pathways,” she told us.
“In this study, the biased agonists were made to stimulate mu opioid receptor signalling through a pathway associated with pain relief and away from a pathway associated with respiratory suppression.”
Out of approximately 500 compounds developed, the researchers found more than 60 that showed bias between signalling assays, and then selected six that represented a wide range in the degree of bias, to determine their overall potency for inducing pain-relief and respiratory suppression.
The ‘bias’ spectrum
Bohn said separating the receptor’s ability to engage in the two pathways enables desired drug effects to disconnect from side effects.
“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,” she said in a statement.
“I think what we have done here is shown that bias isn’t all or none – that there is a spectrum,” she added.
The Institute is still in the fundraising stage, which Bohn hopes will progress the study into clinical trials.
Bohn did not disclose if the Institute is looking to license out the technology.
"We are considering options," she told us.