Search for safer pain relief advances with new engineered compounds

Very good news! This new engineered analgesic is almost a wonder drug! Are we finally coming closer to effective pain medication without or with significantly reduced negative side effects of respiratory suppression, toleration, dependence, and addiction!

"Scientists ... have created a collection of new pain-relieving compounds that, like morphine and other drugs, provide relief via activation of opioid receptors, but without inducing many dangerous and unwanted side-effects that have driven opioid-related overdose and deaths. ...
describe a compound called SR-17018, which activates the same pain-relieving receptor as opioid drugs including morphine, oxycodone and fentanyl; however it binds to opioid receptors in a different way from those drugs, leaving the opioid receptor open and available to the body’s own natural pain-relieving substances, apparently augmenting pain relief. In a study published earlier this year ..., the group showed that the compound performed particularly well in mouse studies of chemotherapy-induced neuropathic pain, the scientists write. ...
Importantly for safety, this compound, SR-14968, proved responsive to overdose rescue medication naloxone ...

the new compounds are referred to as “biased agonists,” because they activate the mu opioid receptor in a way that preferentially engages one of its signaling pathways, the one that provides pain relief, over other pathways such as those that lead to suppressed breathing.

“The compound SR-17018 is the first biased agonist of the mu opioid receptor that does not lead to tolerance with chronic use,” ...

The new compounds were engineered to avoid the “beta-arrestin” signaling cascade that leads to opioids’ dangerous and unwanted traits, including respiratory suppression, a cause of overdose, and constipation, he adds. ...

In work spanning more than two decades, ... [the] team have demonstrated the feasibility of untangling the pain-relieving properties of opioids from their negative traits. ...
The compound showed a nice, slow tapering. That, in itself, may help curb some of the dependence problems. A drug like morphine provides a quick rush then a quick clear, and you need the rush again ..."

Search for safer pain relief advances with new engineered compounds | Scripps Research Chronic use of most opioids causes tolerance; the new compounds avoid this and other unwanted qualities.

G protein signaling–biased mu opioid receptor agonists that produce sustained G protein activation are noncompetitive agonists (no public access)