Opioids are commonly used to manage severe pain but pose risks such as addiction, withdrawal symptoms, and overdose. Researchers have discovered a way to design safer opioids by creating an experimental opioid that targets a unique spot in the receptor, reducing harmful side effects including fatal overdoses.
Opioid medications work by activating pain-suppressing receptors in the brain. However, they can lead to physical dependency and dangerous side effects like slowed breathing. Efforts to develop safer opioids have focused on finding molecules that bind outside the typical active site on the receptor.
An earlier study revealed a molecule called C6 guano that activates the opioid receptor at a different location interacting with sodium ions. To improve upon this discovery, a team led by Susruta Majumdar, Jay McLaughlin, Haoqing Wang, and Ruth Huttenhain sought to find a similar molecule that could reach the brain by passing through the blood-brain barrier.
After evaluating 10 compounds, they identified a promising candidate, RO76, derived from fentanyl. RO76 produced a unique signal within cells and showed pain-suppressing effects comparable to morphine but with lesser impact on breathing rates and withdrawal symptoms in mice.
The researchers suggest that RO76 could potentially be developed as an oral medication for humans due to its effectiveness and lower risk profile. This innovative approach to opioid design holds promise in enhancing the safety and efficacy of pain management.
Funding for this research was provided by the National Institutes of Health and the Pharmaceutical Research and Manufacturers of America Postdoctoral Fellowships. Some authors also disclose financial interests with biopharmaceutical companies.
