AT-121: A Promising Alternative to Opioid Pain Medications

By Eric Sarlin, M.Ed., M.A.
NIDA Notes Contributing Writer
National Institute on Drug Abuse

Dr. Eric Sarlin’s recent research reveals an experimental compound with a dual action at two opioid receptors which may provide powerful pain relief without many of the usual harmful opioid side effects. The compound may also have potential as a treatment for opioid addiction.

The reason AT-121 is promising is because it provides pain relief without producing the side-effect of euphoria.

This is a novel compound representing potential advancement toward the goal of non-addictive pain medications that are at least as effective as opioids but without typical opioid liabilities. The new compound—called AT-121—may also have potential as a treatment alternative for opioid addiction. Most of the potent analgesics currently in use act through mu-opioid receptors. AT-121 seems to relieve pain in monkeys without causing physical dependence. Most pain medications work by activating a receptor in the neurons the mu-opiate receptor. Mei-Chuan Ko, a professor of physiology and pharmacology at the Wake Forest School of Medicine, says “Oxycodone, morphine, fentanyl, heroin—they all work through the mu-receptor.” Ko is one of the authors of the study.

Dr. Nurulain Zaveri and colleages at Astraea Therapeutics, manufacturer of AT-121, used medicinal chemistry, computer modeling, and structure-based drug design to create and develop AT-121. Like opioids—such as morphine and oxycodone—AT-121 also binds to the mu-opioid receptor. Unlike those opioids, AT-121 also binds to another opioid receptor called the nociceptin/orphanin FQ peptide receptor. According to Dr. Zaveri, this interaction with the NOP receptor enhances AT-121’s analgesic effect and blocks unwanted side effects often seen with current opioid medications.

References

NIDA. (February 12, 2019). “A Promising Alternative to Opioid Pain Medications.”

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