New Opioid Form Reduces Addiction Risk

The drug PZM21 could potentially provide pain relief without addiction risk.

Researchers in a recent study created an opioid that could potentially be safer and reduce overdoses.

In a study published in Nature, researchers discovered the atomic structure of the morphine receptor in the brain, called the mu-opioid receptor. They then created a drug that can block pain as efficiently as morphine, without the side effects.

The experimental drug does not activate the brain’s reward region, giving it the potential to reduce addiction.

“There are so many medical procedures we can do now because we know we can control the pain afterwards. But it's obviously dangerous too,” said co-senior author Brian Shoichet, PhD. “People have been searching for a safer replacement for standard opioids for decades.”

The recent opioid epidemic caused significant legislative efforts regarding prescribing practices, but a new pain treatment that reduces the likelihood of addiction could be the answer to the crisis. Rather than alter the structure of morphine, researchers developed a new opioid from scratch using information about the structure of the mu-opioid receptor, according to the study.

“With traditional forms of drug discovery, you're locked into a little chemical box,” Dr Shoichet said. “But when you start with the structure of the receptor you want to target, you can throw all those constraints away. You're empowered to imagine all sorts of things that you couldn't even think about before.”

Researchers combined structural information about the receptor with molecular docking, a computational technique. Through this method, researchers were able to conduct 4 trillion virtual experiments, and then simulated how 3 million molecules could fit and activate the mu-opioid receptor.

The researchers were looking for a molecule that can bind to and activate the G-protein, but did not activate beta-arrestin2, so the drug can reduce pain without causing respiratory problems and constipation. They were able to discover 23 promising molecules and, eventually, discovered that PZM21 was the most effective candidate.

In mice studies, the drug was able to reduce pain as effectively as morphine, but did not cause the side effects. This molecule was also able to specifically target opioid circuit in the brain without activating the receptors in the spinal cord.

The researchers said that no other opioid was that selective. Additionally, they found that PZM21 did not stimulate dopamine pathways in the brain. These pathways are associated with opioid addiction.

The investigators also discovered that mice did not show drug-seeking behavior.

“We haven't shown this is truly non-addictive,” Dr Shoichet said. “At this point we've just shown that mice don't appear motivated to seek out the drug.”

The researchers said they are on the right path to create a drug that could curb opioid addictions, and fight the epidemic.