Researchers build a better opioid painkiller from scratch

The new compound could reduce overdoses and possibly curb addiction, while addressing the needs of millions of people suffering with chronic pain.

Researchers build a better opioid painkiller from scratch click to enlarge Bryan Roth, MD, PhD (photo by Max Englund, UNC Health Care)

August 17, 2016

CHAPEL HILL, NC – An international research team – led by scientists at UC San Francisco, Stanford University, the University of North Carolina (UNC), and the Friedrich-Alexander University Erlangen-Nürnberg in Germany – has developed a new opioid drug candidate that blocks pain without triggering the dangerous side effects of current prescription painkillers. Their secret? They started from scratch.

In a new study published today in Nature, the researchers used the newly deciphered atomic structure of the brain’s “morphine receptor” to custom-engineer a new drug candidate that blocked pain as effectively as morphine in mouse experiments but did not share the potentially deadly side effects typical of opioid drugs, including morphine and oxycodone. In particular, the new drug did not interfere with breathing – the main cause of death in overdoses of prescription painkillers as well as street narcotics like heroin – or cause constipation, another common and sometimes severe opioid side effect. In lab tests, the new drug also appeared to side-step the brain’s dopamine-driven addiction circuitry and did not cause drug-seeking behavior in mice.

More work is needed to establish that the newly formulated compound is truly non-addictive and to confirm that it is as safe and effective in humans as it is in rodents, the authors said. But if the findings are borne out, they could transform the fight against the ongoing epidemic of prescription painkiller addiction.

Read how they did it in the full article on SOM News by Marc Derewicz

Read the Nature article, "Structure-based discovery of opioid analgesics with reduced side effects," published today.

Lead authors on the new paper were Aashish Manglik, MD, PhD, of Stanford University School of Medicine; Henry Lin, PhD, of the UCSF School of Pharmacy; and Dipendra K. Aryal, PhD, of the UNC School of Medicine.