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Scientists Take big Step Toward Finding Non-Addictive Painkiller:
With the support of the National Institute on Drug Abuse, scientists at Wake Forest School of Medicine have been working to find a safe, non-addictive pain killer to help fight the current opioid crisis in this country.
And they may have done just that, though in an animal model.
Known as AT-121, the new chemical compound has dual therapeutic action that suppressed the addictive effects of opioids and produced morphine-like analgesic effects in non-human primates.
"In our study, we found AT-121 to be safe and non-addictive, as well as an effective pain medication," said Mei-Chuan Ko, Ph.D., professor of physiology and pharmacology at the School of Medicine, part of Wake Forest Baptist Medical Center.
"In addition, this compound also was effective at blocking abuse potential of prescription opioids, much like buprenorphine does for heroin, so we hope it could be used to treat pain and opioid abuse."
The findings are published in the Aug. 29 issue of the journal Science Translational Medicine.
The main objective of this study was to design and test a chemical compound that would work on both the mu opioid receptor, the main component in the most effective prescription pain killers, and the nociceptin receptor, which opposes or blocks the abuse and dependence-related side effects of mu-targeted opioids. Current opioid pain drugs, such as fentanyl and oxycodone, work only on the mu opioid receptor, which also produces unwanted side effects -- respiratory depression, abuse potential, increased sensitivity to pain and physical dependence.
"We developed AT-121 that combines both activities in an appropriate balance in one single molecule, which we think is a better pharmaceutical strategy than to have two drugs to be used in combination," Ko said.
In the study, the researchers observed that AT-121 showed the same level of pain relief as an opioid, but at a 100-times lower dose than morphine. At that dose, it also blunted the addictive effects of oxycodone, a commonly abused prescription drug.
[...] "Our data shows that targeting the nociceptin opioid receptor not only dialed down the addictive and other side-effects, it provided effective pain relief," Ko said. "The fact that this data was in nonhuman primates, a closely related species to humans, was also significant because it showed that compounds, such as AT-121, have the translational potential to be a viable opioid alternative or replacement for prescription opioids."
Journal Reference:
- Huiping Ding, Norikazu Kiguchi, Dennis Yasuda, Pankaj R. Daga, Willma E. Polgar, James J. Lu, Paul W. Czoty, Shiroh Kishioka, Nurulain T. Zaveri, Mei-Chuan Ko. A bifunctional nociceptin and mu opioid receptor agonist is analgesic without opioid side effects in nonhuman primates. Science Translational Medicine, 2018; 10 (456): eaar3483 DOI: 10.1126/scitranslmed.aar3483
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(Score: 3, Informative) by EvilSS on Thursday August 30 2018, @07:15PM (2 children)
The other path is physiological dependence. This one can occur whether or not you are susceptible to abusing a drug. This is due to your body trying to maintain homeostasis, and adjusting your neurochemistry to counter a drug you are taking to get your brain back to where it thinks it's supposed to be. This can happen to anyone who is on long term (months, years) opioid therapy. Over time the pain requires higher and higher doses to treat. Patients like this are not getting a "high" but if they try to quit cold turkey, they can have withdrawal symptoms and the pain is usually unbearable. Often tapering the patient off the drugs is successful, and many realize when they are off them that they really no longer even need them. It's just that being on them for so long was causing their brains to boost the pain signals to compensate for the effects of the drug.
(Score: 0) by Anonymous Coward on Thursday August 30 2018, @11:23PM (1 child)
I use to be in the opiate are about as fun as aspirin camp and I had hydromorphone I.M. once it was the most enjoyable experience I ever had. Yet, I experience that indescriptible bliss after dental surgery that required them to break my jaw to extract a wisdom teeth. I am pretty sure that IV administred opiates are radically addictive.
(Score: 2) by HiThere on Friday August 31 2018, @01:39AM
My wife didn't find opiates addictive after heart surgery. OTOH, she also had a strong pain suppression to even a small dosage, and additionally often took a lot longer than expected to recover consciousness after a general anesthetic. Etc. Her liver didn't degrade certain chemicals well.
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