Morphine Hydrochloride Hydrate

In an effort to identify a more universal treatment for drug overdose, a team of scientists tested a chemical compound -- Pillar[6]MaxQ (P6AS) -- as an antidote for methamphetamine and fentanyl. Their findings were highly promising. Drug overdoses in the United States have risen sharply in the last two decades. Nearly 92,000 people died from overdoses of illegal drugs and prescription opioids in 2020 -- more than five times the number of deaths in the year 2000 -- and synthetic opioids like fentanyl are one of the main culprits. Naloxone (an injectable medicine also marketed as the nasal spray Narcan) has saved countless lives, but it only works for opioid overdoses and has other limitations. Now, in an effort to identify a more universal treatment for drug overdose, a team of University of Maryland scientists tested a chemical compound -- Pillar[6]MaxQ (P6AS) -- as an antidote for methamphetamine and fentanyl. Their findings, published today in the journal Chem, were highly promising. "Opioids already have a reversal agent in naloxone, but 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," said the study's lead author Lyle Isaacs, a professor in the Department of Chemistry and Biochemistry at UMD. "That's one of the huge opportunities for our compound." In vitro and in vivo laboratory tests showed that P6AS successfully sequestered fentanyl and methamphetamine, a non-opioid stimulant, and mitigated their potentially deadly biological effects. Additional in vitro tests revealed that P6AS also binds strongly to other drugs, including PCP, ecstasy and mephedrone, which suggests that P6AS could someday be used to counteract a wide array of drugs. The study was conducted by Isaacs' lab in collaboration with researchers in UMD's Department of Cell Biology and Molecular Genetics and Department of Psychology. Although the synthesis and chemical properties of P6AS were first documented in 2020 by Isaacs and Weijian Xue, a former post-doctoral associate in the Department of Chemistry and Biochemistry, this study reports its first in vivo applications. P6AS works as a molecular container, which means that it binds and sequesters other compounds in its central cavity. "When we put molecules into our containers, we can turn off their biological properties and thereby reverse any effects that they might have," Isaacs explained. "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." In vivo tests revealed that the effects of methamphetamine could be reversed by administering P6AS five minutes later, which is "still a little bit short for real-world situations," Isaacs explained. The effects of fentanyl, however, could be reversed by administering P6AS up to 15 minutes later, which comes closer to meeting the federal guidelines for drug reversal agents. 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. "Our compound soaks up the drug in the bloodstream and, we believe, helps promote its excretion in the urine," Isaacs said. "This is known as a pharmacokinetic process, where we're trying to minimize the concentration of free drug that's present in the body." Whether this compound helps promote a drug's excretion from the body must be tested experimentally. If it performs in the way that researchers think it will, it could be particularly useful for overdoses of fentanyl, which is up to 50 times stronger than heroin and up to 100 times stronger than morphine. Its potency and lingering effects in the body explain why some patients continue to overdose even after receiving naloxone. Isaacs believes that the excretion of fentanyl could help prevent this phenomenon, known as renarcotization. Isaacs said it will likely be years before the new compound is approved for human use. However, he envisions that 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 a string of overdose deaths in recent years. "There are other synthetic opioids that are much stronger than fentanyl -- things like carfentanil, which are difficult to reverse using naloxone," Isaacs said. "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."

Researchers have modified a yeast cell to sense the active substances in cannabis and get it to turn red when it does. The result paves the way for more actors to discover new medicinal substances and for a new type of drug test that can be done with a smartphone. Researchers at the University of Copenhagen's Faculty of Science have modified a yeast cell to sense the active substances in cannabis and get it to turn red when it does. The result paves the way for more actors to discover new medicinal substances and for a new type of drug test that can be done with a smartphone. Yeast cells are simple organisms. They do two things in life: eat and propagate. Now, researchers at the University of Copenhagen's Department of Plant and Environmental Sciences have equipped common baker's yeast cells with a new function. The researchers substituted the yeast cell's sex drive with a sense of taste and smell that allows it to detect cannabinoids, the active substances in cannabis. Going one step further, the researchers made the yeast turn red or glow when it successfully detects cannabinoids. The study has been published in Nature Communications. "We have made a living sensor out of the yeast cell, which can now sense cannabinoids or molecules that have the same function as cannabinoids even if they look very different than cannabinoids. Among other things, the biosensor can be used to look for new substances with the same properties as cannabinoids. This could democratize medicinal development so that pharmaceutical companies aren't the only ones equipped to discover new substances," says Professor Sotirios Kampranis of the Department of Plant and Environmental Sciences, who headed the research. Turns red when sensing cannabinoids Humans use hundreds of different GPCRs (G-protein-coupled receptors) to taste and smell. In our noses alone, 400 different GPCRs make it possible for us to detect and distinguish between the smell of roses and freshly baked bread, each of which activates different GPCRs that then signal the brain. Along with his research colleagues, Professor Kampranis swapped the GPCR that yeast cells use to sense the opposite sex in an environment, with the GPCR we humans use to recognize cannabinoids. At the same time, the researchers complemented the yeast cell's genetic material with a set of new genes that make it turn red or even glow when it senses cannabinoids nearby. "The yeast cell now emits a signal when there are cannabinoids in the yeast cell's environment. This allows us to screen thousands of plants for substances with therapeutic potential. And we can also investigate whether people are on drugs or whether someone is trying to smuggle illegal cannabinoids or "designer drugs" through an airport checkpoint," explains Professor Sotirios Kampranis. Discovered four new substances in one day Cannabinoids are known to be connected with sleep, appetite and pain relief. In fact we have them naturally in our bodies where they are calle endocannabinoids. This is precisely why the researchers chose to encode the ability to find cannabinoids in the yeast cells. But in principle, they could have done so for opioids or any other group of medicinal substances.This is precisely why the researchers chose to encode the ability to find cannabinoids in the yeast cells. But in principle, they could have done so for opioids or any other group of medicinal substances. There is no doubt that the yeast cell can find new substances. In initial tests, the researchers used the yeast cell to study 1600 random substances from a vast chemical compound library available at the University of Copenhagen. It didn't take long to get a bite. "In a single day, the yeast cell found four undiscovered substances that had never been associated with anti-inflammatory properties or pain relief, but could potentially be used for these purposes," says Sotirios Kampranis. When drug companies look for new drugs today, it is with the help of state-of-the-art robotics and laboratory equipment that universities and other non-commercial entities will never be able to afford. That the researchers have developed an alternative, may allow for more people to hunt for helpful substances in nature. "It's a crowdsourcing approach whereby smaller laboratories can find more new potential substances for pharmaceutical use. I don't see it as competition with pharmaceutical companies -- but as something that can create a synergy between independent players in the scientific world and the pharmaceutical industry," says Professor Kampranis. Smartphone accessory can find drugs The researchers also developed a portable plastic device with a yeast cell biosensor in it. Plant material, saliva, urine, blood, material from a suitcase, or whatever one would like for the yeast cell to test, is placed into the gizmo. The device then uses the smartphone's camera to see if the yeast cells light up, delivering its result in just 15 minutes. The application could be able to help police officers and others track down drugs at airports or administer drug tests. "We can test for both natural cannabinoids and designer drugs -- chemical substances that have very different structures -- with the same effects as cannabinoids. In principle, we could also adapt the yeast cell to be able to detect opioids like morphine, fentanyl and oxycodone," says Sotirios Kampranis. The device can be 3D printed or assembled using materials easily obtained online. The researchers are now working to make the test tool available free of charge, for as many people as possible, but at the same time be able to maintain control for maintenance and further development.