One of the best -selling painkillers on the planet, Paracetamol, the active ingredient of Tylenol, has been used in the last 70 years to relieve pain and reduce people’s fever. However, to this day, no one has fully understood its mechanism of action.
Now, a new pharmacological study by researchers at the University of Indiana (IU) showed that the drug does not relieve pain by increasing natural chemicals associated with well-being, as thought, but reducing one of them.
the work had as research problem an important paradox: although the acetaminophen causes about 500 annual deaths from overdose in the United States, no safer alternatives have not yet been developed to replace it.
As there is evidence that endocanabinoids, molecules that modulate the perception of pain, can play a role in the action of acetaminophen, the study sought to examine this pharmacological interaction.
The results revealed an entirely unprecedented mechanism on how the drug acts against pain, eventually making way for the development of new, more effective and less risk of toxicity.
How do endocanabinoids work in pain relief?
Discovered by chance in the early 1990sWhen neuroscientists investigated how Marijuana’s THC (tetra-hydrocanabinol) acted in the human body, the endocannabinoid system acts as an internal communication network of our body, consisting of three main elements.
First, there are receptors, a kind of cellular “antennas” that capture chemical signals. There are also endocanabinoids, molecules that carry messages between cells, and the enzymes that produce and degrade these messengers, after they have fulfilled their function in the body.
This structure acts as a “modulator system” that maintains balance (homeostasis) in processes such as pain, mood, appetite, sleep, immune response and memory. Retroges, endocanabinoids are produced “on demand” by the postsynaptic cell and travel back to modulate the pre-synaptic cell.
“So far, we thought that high endocanabinoids in our body meant less pain, but our study shows that in the case of [endocanabinoide] 2-ag, it can be the opposite. , explains the first author, Michaela Dvorakova, in a statement.
According to the authors, acetaminophen blocks the enzyme responsible for the production of 2-araquidonoil glycerol, or 2-ag. This natural cannabinoid active body receptors known to influence pain, mood and even the effects of cannabis.
A safer version of acetaminophen?
The scientific community believed that acetaminophen worked by increasing natural endocanabinoid levels in the body, substances that activate CB1 receptors in the brain, the same stimulated by cannabis psychoactive compounds to relieve pain.
For co -author, Alex Straiker, a researcher at the Gill Institute (IU Neuroscience Research Center), 50 years of studies have consolidated the idea that receptor activation, later known as CB1, produces pain relief, creating a kind of “scientific dogma,” he explains in a statement.
Completely challenging these established beliefs, the new study showed that acetaminophen actually inhibits the enzyme responsible for the production of 2-Ag. Paradoxically, the suppression of the enzyme (with “shutdown” of the CB1) resulted in less pain for the mice of the experiment.
: In addition to hundreds of deaths, the drug overdose is the second main cause of liver transplantation around the world. Therefore, the authors say, understanding their mechanisms of action has become so urgent.
The great difficulty so far, says Straiker, was to identify the target. “Our research suggests that this enzyme can be the targetIn case you can start developing medicines that target this specific enzyme, but without this toxicity, “celebrates the neuroscientist.
