American Chemical Society Conference reveals several new opioid drugs that offer pain relief with far less risk of addiction or overdose.
According to a report published by the Centers for Disease Control and Prevention (CDC), in August 2018, around 72,000 people in the U.S died from overdoses in 2017, which was nearly 10% from 2016. Opioids bind to the µ-opioid receptor (MOR) –a key cell membrane protein that is located on neurons in the brain and spinal cord. The MOR triggers an intracellular ‘G protein’ when activated that initiates a molecular cascade and reduces pain. However, conventional opioids also activate another intracellular protein called as β-arrestin2, which produces respiratory depression and constipation.
Neel Anand, a senior director for medicinal chemistry at Nektar Therapeutics, described a new approach at the American Chemical Society Conference held in Boston during August 19-23, 2018. NKTR-181, a version of oxycodone developed by Nektar has a molecular tail called polyethylene glycol, which is a common pharmaceutical strategy for extending the life span of medicines in the blood. NKTR-181, in animal studies successfully crossed the blood-brain barrier 70 times more slowly than oyxcodone. The drug triggers a slower release of dopamine to facilitate more sustained pain relief and less euphoria. Moreover, fewer signs of addiction and side effects were associated with NKTR-181 compared to oxycodone in clinical studies of over 600 patients taking the compound.
Furthermore, Astraea Therapeutics, a biotech company in Mountain View, CA has developed AT-121 that hits two brain molecules at once. The drug stimulates both MOR and nociceptin opioid receptor (NOR). NOR appears to counteract MOR when activated in the brain and the receptor reinforces MOR’s pain relieving activity elsewhere in the central nervous system. However, the drug targets other receptors as well and may have addictive properties. In an experiment with rhesus monkeys, AT-121 resulted in 100-fold greater pain relief compared to same dose of morphine. Moreover, drug did not trigger respiratory depression and addictive-like behaviors in the monkeys. The dug appears to counteract addiction to standard opioid as it was evident with the monkeys hooked on oxycodone.