Discovered pain reliever without side effects as a morphine substitute

Discovered pain reliever without side effects as a morphine substitute

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Drug PZM21 relieves severe pain without negative side effects
Morphine is a pain reliever that is only approved for severe pain. Overdosing on the drug can be life-threatening and morphine can also quickly become addictive to patients. Researchers have now found that a synthetic drug works just as effectively against pain, but without the typical side effects and fast-developing addiction to opioids.

An international team of scientists from the University of California at San Francisco, Stanford University and the Friedrich Alexander University in Erlangen-Nuremberg found that a new synthetic drug can fight the pain as effectively as morphine. With the new drug called PZM21, there is no risk of becoming addicted. The doctors published the results of their study in the journal "Nature".

PZM21 does not slow down or block breathing
A study in mice found that the new substance activates a known molecular signaling pathway in our brain that triggers pain suppression. But unlike pain relievers like morphine and prescription drugs like oxycodone or oxycontin, it doesn't slow or block our normal breathing, the researchers explain.

Opioid use and abuse has reached epidemic proportions
The use of opioids results in about 30,000 deaths each year in the United States alone, by attenuating the respiratory center, the authors say. The ever-increasing overdose of opioid painkillers is also killing more and more people. Consumption and abuse has now reached epidemic proportions in the United States, doctors warn.

PZM21 is not addictive
The new drug PZM21 was not addictive to laboratory mice, although morphine and other pharmaceutical painkillers addict mice as quickly as we humans, the scientists explain. In the experiments, the rodents showed no preference between PZM21 or an administered neutral saline solution.

New drug does not slow down breathing and does not cause constipation
PZM21 offers long-lasting analgesia (pain therapy) and does not slow down our breathing. In addition, the drug does not cause constipation, the scientists explain. In the United States, there are now extra drugs designed to relieve the intestine clogged with opioids.

Opium and its derivatives are still the main pain reliever for severe pain
For the past 4,000 years, people have used opium and its derivatives to combat pain and create euphoric feelings. Even in our age of modern medicine, morphine remained the main pain reliever for severe pain, say the experts. The substance derived from the opium poppy is used, for example, for recovery after operations or for the immediate treatment of severe wounds and pain.

The search for a safe replacement for opioids has been going on for decades
The dangers of opium are obvious, says author Professor Brian Shoichet from the University of California School of Pharmacy. People need a safe replacement for opioids. The search for it has been going on for decades, the expert adds. Most efforts have been aimed at optimizing the chemical structure of the drug. This should eliminate the side effects.

Researchers are focusing on opioid receptors in the brain
But researchers at Stanford University, the University of North Carolina, and Friedrich Alexander University in Germany used a different radical approach to problem solving. They focused on the so-called opioid receptors in the brain, which trigger a chemical reaction to suppress pain when activated.

Doctors are taking a new route to problem solving
The medical team was looking for a molecule that can successfully dock onto a receptor without docking onto a second receptor. Docking on the second receptor triggers the unwanted reaction of drug addiction, the scientists explain. The traditional forms of drug discovery don't really help here. However, when the doctors started with the structure of the receptor to be addressed, there were hardly any restrictions in the examinations.

Computer simulations examined three million commercially available connections
Using computer simulations, the researchers examined three million commercially available connections and additionally considered one million possible configurations for each connection. So they wanted to determine which configuration worked best with the receptor. In a laboratory experiment, the costs of examining trillions of configurations would have been prohibitively expensive and, in addition, very time-consuming, the researchers explain.

Examinations are the first step in developing the perfect pain reliever
Finally, the scientists found an active ingredient that showed in further analyzes that it triggered the good molecular signaling pathways but did not activate any negative signaling pathways. The new investigation was a first step towards developing a perfect medication for pain, the experts say. However, PZM21 still has many hurdles to overcome before it is available as a drug in our pharmacies.

More research is urgently needed before the drug comes onto the market
Further clinical studies have yet to prove that PZM21 is safe for humans. This process can typically take up to a decade, the scientists explain. Future research must also show whether the drug leads to tolerance or resistance in humans or mice. Such a drug could lose its analgesic effect over time, the experts add. (as)

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Video: Opioid Addiction and its Treatment. Dr. Belis Aladag - UCLA Health (May 2022).