PZM21 Could Enable Painkiller Without Addiction Risks

Posted: Aug 18 2016, 4:50am CDT | by , in Latest Science News


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PZM21 Could Enable Painkiller Without Addiction Risks

An international team of researchers has developed an experimental new opioid drug that blocks pain without triggering the dangerous side effects of current prescription painkillers, including addiction risk.

In a study published in the journal Nature, the researchers demonstrated that the novel drug candidate blocked pain as effectively as morphine - a common painkiller -- 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.

"We haven't shown this is truly non-addictive," cautioned co-senior author Brian Shoichet, Professor at University of California San Francisco, emphasizing that further experiments in rats and humans would be needed to establish the compound's addictive potential.

"At this point we've just shown that mice don't appear motivated to seek out the drug," Shoichet noted.

In addition, the compound PZM21 appeared to dull pain by affecting opioid circuits in the brain only, with little effect the on opioid receptors in the spinal cord that mediate pain reflexes.

No other opioid has such a specific effect, Shoichet said, calling it "unprecedented, weird and cool."

Their secret? Starting from scratch -- with computational techniques that let them explore more than four trillion different chemical interactions.

"This promising drug candidate was identified through an intensively cross-disciplinary, cross-continental combination of computer-based drug screening, medicinal chemistry, intuition and extensive preclinical testing," study co-senior author and 2012 Nobel laureate Brian Kobilka, Professor at the Stanford University School of Medicine, said.

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