Newly created chemical compounds can reverse the effects of potentially deadly drugs

Their method successfully counteracted two highly addictive drugs in lab experiments.

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Drug overdoses have risen in the last two decades. More than five times as many people died in the year 2000 from drug overdoses, and synthetic opioids like fentanyl are one of the leading causes. In 2020, about 92,000 individuals died from overdoses of illegal drugs and prescription opioids.

Nalozone has saved countless lives, but it only works for opioid overdoses and has other limitations. Opioids already have a reversal agent in naloxone. Still, there are a variety of non-opioid drugs of abuse—like methamphetamine, PCP, mephedrone, ecstasy (MDMA), and cocaine—that do not have a specific antidote.

To identify a universal treatment for a drug overdose, a team of University of Maryland scientists tested a chemical compound—Pillar[6]MaxQ (P6AS)—as an antidote for methamphetamine and fentanyl.

P6AS successfully sequestered a non-opioid stimulant called methamphetamine and fentanyl in vitro and in vivo experiments, and their potentially fatal biological effects were reduced. P6AS also significantly attaches to other substances, such as PCP, ecstasy, and mephedrone, according to additional in vitro testing, which raises the possibility that P6AS may one day be used to block a variety of drugs.

Study’s lead author Lyle Isaacs, a professor in the Department of Chemistry and Biochemistry at UMD, said, “When we put molecules into our containers, we can turn off their biological properties and thereby reverse any effects that they might have. We’ve measured the interaction between our container and a variety of drugs of abuse—things like methamphetamine, fentanyl, ecstasy, PCP, and others—and we find that this new container that we’ve made binds many of them very strongly.”

P6AS successfully sequestered a non-opioid stimulant called methamphetamine and fentanyl in vitro and in vivo experiments, and their potentially fatal biological effects were reduced. P6AS also significantly attaches to other substances, such as PCP, ecstasy, and mephedrone, according to additional in vitro testing, which raises the possibility that P6AS may one day be used to block a variety of drugs.

Unlike naloxone, which stops a drug of abuse from binding to receptors in the brain, the UMD team’s molecular container targets drugs directly in the bloodstream.

Isaacs said, “Our compound soaks up the drug in the bloodstream and, we believe, helps promote its excretion in the urine. This is a pharmacokinetic process, where we’re trying to minimize the concentration of free drug in the body.”

Experimental testing is required to determine whether this chemical facilitates a drug’s elimination from the body. If it works as expected, experts believe it will be especially helpful for fentanyl overdoses, which may be up to 100 times more potent than morphine and up to 50 times stronger than heroin. Some individuals continue to overdose even after using naloxone, which is due to its potency and persistent effects on the body. According to Isaacs, fentanyl excretion may stop this condition, known as narcotization.

Isaacs said“It will likely be years before the new compound is approved for human use. However, he envisions it could be delivered as an injection, much like naloxone but potentially with broader applications. Isaacs believes it could even be used to treat overdoses of extremely powerful drugs like carfentanil, which has been linked to numerous overdose deaths in recent years.”

“There are other synthetic opioids that are much stronger than fentanyl—like carfentanil, which are difficult to reverse using naloxone. In addition, people are getting so much fentanyl that multiple doses of naloxone are needed, so there’s room for a new and improved agent that might help in those situations.”

Journal Reference:

  1. Adam T. Brockett et al. Pillar[6]MaxQ: A potent supramolecular host for in vivo sequestration of methamphetamine and fentanyl. Chem. DOI: 10.1016/j.chempr.2022.11.019

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