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Non-additive Opioid Alternative Shows Promise in Monkey Study



With the opioid epidemic raging across America, many scientists are looking for an alternative analgesic drug that could be used instead of opioids without the deadly side effects.

Now a team of researchers in the US and Japan said they have developed a promising new synthetic drug that could be just as effective at relieving pain as opioids, but without the risk of dependence. In a new study, the drug called AT-121 successfully alleviated the pain in rhesus monkeys without causing harmful side effects or causing addiction to monkeys. More research is needed before the drug could be evaluated in humans.

"I think that's pretty interesting," Dr. Bryan Roth, a professor of pharmacology and a doctor at the University of North Carolina at Chapel Hill, who was not involved in the study. "The results are really clear, but there are still a few things that still need to be done before it can go on," he said.

Although the number of opioids prescribed in the US has fallen since its peak in 201

0, the level remains high. The Center for Disease Control and Prevention (CDC) found that there were more than 42,000 deaths from opioid overdose in 2016 compared to 33,000 deaths in 2015, Live Science previously reported. [America’s Opioid-Use Epidemic: 5 Startling Facts]

"It's a huge problem, I do not think anyone disagrees," Roth told Live Science.

AT-121, according to Bf's study, means that it addresses and prohibits the function of two specific opioid receptors in the brain that inhibit the sensation of pain: the mu-opioid peptide (MOP) receptor and the Nociceptin / orphanin FQ peptide (NOP) receptor. Similar drugs have been studied in experiments with mice, and although these drugs effectively relieved pain, they were addictive and therefore not viable alternatives to existing opioid analgesics.

"This is the first [painkiller drug] that was demonstrated in a nonhuman [primate] model to have such a promising profile," said co-senior author Mei-Chuan Ko, a professor of physiology and pharmacology at Wake Forest University in North Carolina, opposite Live Science.

The team tested the drug in 15 years of male and female rhesus monkeys ( macaca mulatta ). In a series of experiments, the researchers found that monkeys given AT-121 did not feel pain and did not have the typical side effects associated with similar drugs.

"The pain relief that was observed in [animal experiments] was similar to that of morphine, but the dose of AT-121 that was used was 100-fold lower than that of morphine," said co-senior study Author Nurulain Zaveri, president and chief scientific officer at Astraea Therapeutics, a pharmaceutical company involved with the study.

The drug not only relieved the pain, but the monkeys were also not dependent on it. If the monkeys were given the ability to self-administer AT-121, they repeatedly chose not to do so. This suggests that AT-121, at least in this short-term experiment, does not produce a rewarding or potentiating effect that would lead to addiction.

The fact that the drug was studied in a primate model and not in a mouse. Emagazine.credit-suisse.com/app/art … = 120 & lang = DE As many similar studies show, This means that the effect of the drug is likely to be much closer to what scientists would expect, Roth said. And the monkeys did not experience any changes in respiratory health while taking AT-121, suggesting that an overdose is unlikely to cause the harmful or fatal respiratory effects associated with opioid overdose. "That would be a significant step forward if [result] were transferable to humans," Roth added.

One of the limitations of the study was that it did not look at so-called off-target activity, Roth said. This refers to drug interactions with other parts of the brain or areas outside the brain. "It's very important to find out – does [AT-121] work with other receptors or ion channels or transporters in the body?" Roth said. Such interactions could determine the potential for adverse events outside of those studied in this study.

The scientists plan to continue their research by performing the safety and toxicology studies required by the US Food and Drug Administration before continuing human clinical trials. "We want to move as fast as possible because our results are exciting," Zaveri told Live Science. The scientists are also exploring other compounds that have a similar profile to AT-121, she added.

"If we can really come up with these new types of compounds, they can potentially reduce a lot of medical burden," Ko said. "I assume that this will have a big impact on our society and the global community."

"This is one of several of these types of studies that have recently been published and suggest that there is hope to develop safe medications for the treatment of pain," said Roth. "It gives me hope for the field that we turn a corner."

The researchers published their study today (August 28) in the journal Science Translational Medicine.

Original article about Live Science.


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