An international team wass led by scientists at UC San Francisco, Stanford University, the University of North Carolina (UNC), and the Friedrich-Alexander University Erlangen-Nürnberg in Germany.
Their secret? Starting from scratch - with computational techniques that let them explore more than four trillion different chemical interactions.
In a new study - published online August 17, 2016 in Nature - the researchers used the newly deciphered atomic structure of the brain's "morphine receptor" to custom-engineer a novel 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.
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 opioid side effect.
The new drug also appears 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 say.
But if the findings are borne out, they could transform the fight against the ongoing epidemic of prescription painkiller addiction.
Deaths from opioid drug overdoses have been on the rise in the U.S. for decades. According to the Centers for Disease Control and Prevention, 28,000 Americans died of narcotic overdoses in 2014, four times more than in 1999, with more than half of these deaths involving prescription drugs.
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