Adriana, the safer alternative to opioids like fentanyl.

The notorious and feared fentanyl, which caused a devastating epidemic in the U.S. that led to more than 80,000 overdose deaths and a national public health crisis known as the " opioid crisis ," could have its days numbered.

A team of researchers from Kyoto University (Japan) has discovered a new painkiller that exerts its effect through a completely different mechanism. Their study is published in the journal PNAS .

Clinical development of its drug, ADRIANA, is currently underway as part of an international collaboration.

"If successful, ADRIANA would offer a new, non-opioid-dependent pain management option, significantly reducing opioid use in clinical settings," says researcher Masatoshi Hagiwara .

Opioids like morphine are commonly used for their potent pain-relieving effects. However, they carry the risk of serious adverse effects; to avoid a scenario like the one in the U.S., where frequent prescriptions for the opioid OxyContin triggered a surge in the misuse of synthetic opioids like fentanyl , Japan has strict regulations to ensure these drugs are prescribed only by licensed physicians.

The Kyoto University team sought to mimic the effects of norepinephrine , a substance the body releases in dangerous situations and helps reduce pain. However, substances that mimic it can cause cardiovascular problems.

Researchers discovered that selectively blocking a specific type of receptor (α2B) naturally increased norepinephrine, activating other receptors (α2A) that relieve pain without risking heart disease. Using novel screening technology, they were able to identify the world's first drug capable of blocking only these α2B receptors . Following successful administration of the compound to mice and preclinical studies to evaluate its safety, clinical trials led by physicians at Kyoto University Hospital were conducted.

Both the Phase I trial in healthy volunteers and the Phase II trial in patients with postoperative pain following lung cancer surgery yielded very promising results.

Following these promising results, researchers will initiate a large-scale Phase II clinical trial.