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Medications are available to relieve withdrawal symptoms in convalescent patients, but they cause side effects and may sustain the brain changes that led to the addiction, which can lead to relapse before the end of treatment. New research suggests that a better solution will be on the horizon. Rapastinel, an experimental drug originally developed as an antidepressant, substantially reversed the acute opioid withdrawal signs in rats in just three days.
The results suggest that rapastinel may be helpful in helping to manage withdrawal during the first few critical days after treatment and abstinence from opioid use, according to the researchers.
"We have discovered that rapastinel could be a new treatment for opioid addiction because it effectively reduces the signs of withdrawal and produces no negative side effects," said Julia Ferrante, undergraduate student at the university. from Villanova. with Cynthia M. Kuhn, PhD, Professor of Pharmacology and Cancer Biology at Duke University. "By reducing withdrawal symptoms, the patient feels less discomfort during treatment, and we badume that this would decrease the risk of relapse."
Ferrante will present the research at the annual meeting of the American Society for Pharmacology and Experimental Therapeutics at the 2019 Experimental Biology Meeting, held April 6-9 in Orlando, Florida.
"Our research suggests that new alternatives to standard treatments for opioid dependence may be safer and more effective," Ferrante added. "At present, research on opioid addiction in Rapastinel is only focused on rodents, but if the drug continues to be successfully tested, it could enter clinical trials." to be used in humans. "
Buprenorphine and methadone, the drugs most commonly used to help people stop using opioids, are problematic because they themselves are opioids and can lead to addiction, unpleasant and sometimes dangerous side effects, and often need to be used for months to prevent relapse. Ketamine, which has been proposed as a non-opioid alternative treatment for opioid withdrawal, also has potential for abuse and may cause hallucinations and other adverse effects.
Rapastinel, developed as an antidepressant, binds to the same receptor as ketamine, but at a different site, where it has a milder effect. Although a clinical trial has recently concluded that rapastinel is not effective against depression, tests have shown that it is well tolerated and that it has not been observed. serious side effects.
In the new study, Ferrante and Kuhn modeled opioid dependence in rats and then followed withdrawal signs in groups of rats receiving either rapastinel, ketamine, or saline. On the third day, rats treated with rapastin had significantly less signs of withdrawal than those treated with ketamine or saline, which had approximately equal amounts of withdrawal signs.
To advance to clinical trials in humans, researchers will continue to study the effects of rapastinel at the molecular level and determine if the drug can reduce the risk of relapse. If approved for the treatment of opioid dependence, rapastinel would probably be given intravenously, possibly as an outpatient, Ferrante said. It is unknown how long patients should use rapastinel to fully recover from opioid dependence.
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