The United States is battling an opioid epidemic, but a breakthrough in the field of medicine may finally hold the solution to this problem.

Researchers have developed a new opioid drug candidate that can block pain but which does not trigger the dangerous side effects that often occur with use of current prescription painkillers.

Along with his colleagues, Aashish Manglik from the Stanford University School of Medicine used the atomic structure of the brain's morphine receptor, the mu-opioid receptor, to develop the drug that can block pain as effectively as morphine and similar drugs.

Morphine-like drugs bring about their painkilling effect by binding to these receptors. For the study published in the journal Nature on Aug. 17, the researchers used computer modeling to screen 2,500 compounds that can bind to the mu-opioid receptor without causing the negative side effects.

They eventually found one compound that activated the good molecular pathway without significantly stimulating beta-arrestin2, part of the "bad" biological pathway associated with respiratory suppression and constipation linked with use of opioids. The researchers then tweaked this compound to make it more potent.

In studies involving mice, the researchers found that, despite its painkilling abilities, the drug called PZM21 does not have the same potentially fatal side effects associated with opioid drugs.

The primary cause of a potentially fatal opioid overdose is respiratory suppression, but the researchers found that the new drug did not interfere with breathing and also does not cause constipation, a problem that commonly occurs with opioid use.

"Unlike morphine, PZM21 is more efficacious for the affective component of analgesia versus the reflexive component and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses," the researchers reported. "PZM21 thus serves as both a probe to disentangle μOR signalling and a therapeutic lead that is devoid of many of the side effects of current opioids."

Currently available prescription painkillers come with the risk of addiction, but use of the new drug candidate did not appear to cause drug-seeking behaviors in the study on the mice.

"If you give a mouse a drug that activates its reward pathways like cocaine, amphetamine or morphine, the mice just run around more. In this compound, we saw very little of that," said Manglik.

The researchers, however, admit that more work will be needed to establish that the compound is indeed nonaddictive. Further studies are also required to confirm the safety and effectiveness of the drug on humans.

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