Drug overdose rates have risen over the past two decades. More than five times as many people died of drug overdoses in the year 2000, and synthetic opioids such as fentanyl are one of the leading causes. In 2020, approximately 92,000 people died from overdoses of illicit 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. Yet there are a variety of non-opioid drugs, such as methamphetamine, PCP, mephedrone, ecstasy (MDMA), and cocaine, for which there is no specific antidote.
To find a universal cure for drug overdose, a team of scientists from the University of Maryland tested a chemical compound: Pillar[6]MaxQ (P6AS) – as an antidote to methamphetamine and fentanyl.
P6AS successfully isolated 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 binds to other substances, such as PCP, ecstasy and mephedrone, according to additional in vitro testing, raising the possibility that P6AS could one day be used to block a variety of drugs.
The study’s lead author, Lyle Isaacs, a professor in the Department of Chemistry and Biochemistry at UMD, said: “If we put molecules in our containers, we can switch off their biological properties and thereby reverse any effects. 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’re finding that this new container we’ve created binds many of them very strongly.
P6AS successfully isolated 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 binds to other substances, such as PCP, ecstasy and mephedrone, according to additional in vitro testing, raising the possibility that P6AS could one day be used to block a variety of drugs.
Unlike naloxone, which prevents an abused drug from binding to receptors in the brain, the UMD team’s molecular container targets drugs directly into the bloodstream.
Isaacs said, “Our compound absorbs the drug into the bloodstream and we believe helps to promote its excretion in the urine. This is a pharmacokinetic process, where we try to minimize the concentration of free drug in the body.”
Experimental testing is needed to determine if this chemical facilitates the elimination of a drug from the body. If it works as expected, experts believe it will be especially useful for overdoses of fentanyl, which can be up to 100 times more potent than morphine and up to 50 times more potent than heroin. Some individuals continue to overdose even after using naloxone due to its potency and lingering effects on the body. According to Isaacs, the excretion of fentanyl can stop this condition, known as narcotic.
Isaacs said, “It will probably be years before the new compound is approved for human use. However, he envisions it could be given as an injection, just like naloxone, but possibly with wider applications. Isaacs believes it could even be used to treat overdoses of extremely potent 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 with naloxone. Plus, people are getting so much fentanyl that multiple doses of naloxone are needed, so there’s room for a new and improved drug that could help in those situations.”
Magazine reference:
- 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
