Credit score: Cell Stories Drugs (2025). DOI: 10.1016/j.xcrm.2025.102139
A brand new examine from Indiana College scientists might assist the pharmaceutical trade in higher understanding a well-liked over-the-counter ache reliever: Tylenol.
Michaela Dvorakova, a postdoctoral researcher at IU’s Gill Institute for Neuroscience and the School of Arts and Sciences’ Division of Psychological and Mind Sciences, and Gill Institute analysis scientist Alex Straiker printed the examine in Cell Stories Drugs.
Their discovery, which particulars a beforehand unknown means the drug targets ache, may change how pharmacologists take into consideration treating ache, and assist in designing safer and simpler ache drugs.
The researchers discovered that acetaminophen inhibits an enzyme that makes one of many endogenous cannabinoids, 2-arachidonoyl glycerol, or 2-AG. Endocannabinoids are produced by the physique to activate CB1 receptors, the identical receptor that produces the psychoactive results of hashish.
Although acetaminophen, also called Tylenol or paracetamol, is the commonest ache and fever reliever within the U.S., the way it relieves ache continues to be a thriller.
“There are hypotheses, but we still don’t know precisely how it works,” Dvorakova stated. “Up until now we thought that elevated endocannabinoids in our body meant less pain, but our study shows that in the case of 2-AG, it might be the opposite. Actually, reduced levels of 2-AG leads to decreased pain.”
In excessive doses, acetaminophen may be poisonous to the liver. Acetaminophen toxicity causes about 500 deaths per 12 months within the U.S. and is the second main reason behind liver transplantation around the globe. Attributable to its broad availability and its mixture in different merchandise, greater than 60 million Individuals devour acetaminophen weekly, making it essential to grasp the way it targets ache receptors.
“If you don’t know what the target is, you can’t design an alternative,” Straiker stated. “Our research suggests that this enzyme might be the target, in which case you can start developing drugs that target that specific enzyme but without that toxicity.”
There was skepticism within the analysis neighborhood a couple of new mechanism of motion for acetaminophen, Straiker stated. When 50 years of analysis confirmed that activating CB1 receptors produced ache reduction within the physique, scientists settled on that idea.
“It can be hard to break through that dogma,” Straiker stated.
Going ahead, the analysis crew is trying into evaluating different frequent ache relievers, like ibuprofen and aspirin, to find out whether or not they have related mechanisms of motion.
Extra data:
Michaela Dvorakova et al, Acetaminophen inhibits diacylglycerol lipase synthesis of 2-arachidonoyl glycerol: Implications for nociception, Cell Stories Drugs (2025). DOI: 10.1016/j.xcrm.2025.102139
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