In a significant breakthrough for pain management, Japanese researchers have developed ADRIANA, a novel non-opioid analgesic that could provide powerful pain relief without the risks of addiction and overdose associated with current opioids.
This development comes at a critical time, especially in the United States, where over 80,000 deaths in 2023 were attributed to an ongoing "opioid crisis" fueled by the misuse of drugs like fentanyl and OxyContin.
The research team from Kyoto University was inspired by the body's natural pain-suppression system, which involves noradrenaline and α2A-adrenoceptors. However, directly mimicking this system can cause cardiovascular instability. The team's innovative approach was to develop a compound that selectively blocks a different receptor, the α2B-adrenoceptor. This action elevates natural noradrenaline levels, subsequently activating the pain-relieving α2A-adrenoceptors without the dangerous side effects.
Using a novel screening technology, the team discovered the world's first selective α2B-adrenoceptor antagonist, which became the drug candidate ADRIANA.
After successful non-clinical studies in mice, ADRIANA progressed to physician-led clinical trials at Kyoto University Hospital. Both the Phase I trial in healthy volunteers and the Phase II trial in patients with post-operative pain following lung cancer surgery yielded "highly promising results."
Building on this success, preparations are underway for a large-scale Phase II clinical trial in the United States through a collaboration with BTB Therapeutics, Inc., a venture company originating from Kyoto University.
"As Japan's first non-opioid analgesic, ADRIANA has the potential not only to relieve severe pain for patients worldwide but could also play a meaningful role in addressing the opioid crisis," said corresponding author Professor Masatoshi Hagiwara. The team aims to evaluate ADRIANA's effects on various pain types and ultimately make this treatment accessible to a broader population of patients suffering from chronic pain.