Naloxone is an overdose drug.
A new study has found that an experimental drug, known as compound 368, can significantly enhance the effectiveness of the overdose reversal drug naloxone (Narcan), particularly against potent opioids like fentanyl. Published in the journal Nature, the research shows that compound 368 makes naloxone 7.6 times more effective in inhibiting the opioid response responsible for overdose.
Dr. Susruta Majumdar, co-senior study author and professor at Washington University in St. Louis, explained that while naloxone is a life-saving drug, its effects are limited, often requiring multiple doses to reverse opioid overdoses completely. The study demonstrates that combining naloxone with compound 368 can extend its duration of action and increase its potency by influencing opioid receptor responses.
Opioids such as fentanyl and oxycodone function by activating receptors in the brain, which alleviate pain and induce euphoria but also suppress breathing, leading to fatal overdoses. Naloxone works by blocking these receptors, but its effects wear off relatively quickly, especially compared to the prolonged presence of opioids like fentanyl in the body.
To address this issue, researchers screened millions of molecules to find one that could enhance naloxone’s activity. Compound 368 emerged as the most promising candidate, capable of prolonging naloxone’s effectiveness in the body by up to ten times. It achieves this by binding alongside naloxone to opioid receptors, effectively stabilizing its action.
In animal tests, compound 368 not only prolonged naloxone’s activity but also allowed it to reverse the effects of opioids like fentanyl and morphine at significantly lower doses than usual. Importantly, it did not exacerbate the withdrawal symptoms often experienced by individuals revived with naloxone, which can prompt a return to opioid use to alleviate discomfort.
The researchers, who have filed a patent for compound 368 and related molecules, caution that it will likely take 10 to 15 years before such a drug-enhancing agent for naloxone gains approval. Despite this timeline, they are optimistic that their findings could help preserve naloxone’s effectiveness as new and more potent synthetic opioids continue to emerge, posing increased risks of overdose deaths.
Dr. Majumdar stressed the urgent need for continued development in light of evolving opioid threats, expressing hope that their work will ensure naloxone remains a vital antidote against future opioid challenges.
Discussion about this post