New compound in battle to overcome fentanyl overdoses

The University of Florida is teaming with other schools to develop Compound 368.


  • By Dan Macdonald
  • | 12:00 a.m. September 13, 2024
  • | 4 Free Articles Remaining!
Jay McLaughlin, an associate professor at the University of Florida College of Pharmacy, says that Compound 368, when combined with Narcan, may allow it to last longer in the patient’s body and negate the effects of a fentanyl overdose.
Jay McLaughlin, an associate professor at the University of Florida College of Pharmacy, says that Compound 368, when combined with Narcan, may allow it to last longer in the patient’s body and negate the effects of a fentanyl overdose.
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Fentanyl can be a killer.

But, like most drugs, when used properly by trained medical professionals, it can have positive outcomes. Surgery patients are most likely being sedated with a form of fentanyl.

“Fentanyl is an incredibly potent opioid agonist. It works at the same sites that morphine works at, only it’s about 100-fold more potent,” said Jay McLaughlin, an associate professor at the University of Florida College of Pharmacy.

“Under proper supervision, it will treat your pain after a surgical moment perfectly well, and then it’s going to leave your system and be perfectly clean.”

However, those lacing street drugs with fentanyl aren’t wearing lab coats.

Fentanyl can disable the part of the brain that regulates breathing. Those overdosing on fentanyl stop breathing.

If an overdose victim receives treatment in time, the patient is given naloxone, an opioid overdose reversal drug also known by the brand-name version Narcan. It neutralizes fentanyl’s effects for a short time.

Over-the-counter Narcan nasal spray is a treatment designed to rapidly reverse the effects of a life-threatening opioid emergency.

Time is Narcan’s weakness. It doesn’t last long.

Medical researchers from around the country including the University of Florida in Gainesville have found a promising drug, Compound 368, that when combined with Narcan may allow it to last longer in the patient’s body and negate the effects of the fentanyl overdose.

“We found this compound. We being a large group of really fabulous collaborators – kind of a dream team of scientists – each bringing a different skill set to answering the question, can we find ways to treat opioid overdose more effectively? And they screened a library of 2 billion compounds,” McLaughlin said.

Compound 368 is that discovery.

“Narcan is the treatment we give folks who are experiencing opioid overdose, right? So Narcan will save your life,” he said.

“And we love Narcan because it’s probably one of the safer drugs we’ve ever worked with. It is what is called an opioid receptor antagonist.”

Jay McLaughlin

With the receptor blocked, fentanyl is rendered harmless. However, Narcan leaves the body before fentanyl. When Narcan wears off, receptors reactivate.

Depending on the fentanyl potency, a patient may have to receive numerous separate doses of Narcan to survive the overdose.

The discovery doesn’t mean the Narcan-Compound 368 cocktail is being used yet at UF Health Jacksonville or anywhere else.

Toxicity studies have to be conducted. Independent teams of scientists need to replicate the Compound 368 findings. That work is underway, McLaughlin said.

All of this must be done so safe clinical trials can be conducted.

“I would love to say within 10 years, but it’ll probably be along that time frame,” McLaughlin said.

“We have a new option to give people to help them with this. Having said that, the severity of the problem is such that maybe they’ll find ways to make that go faster.”

Approval is important because more deadly fentanyl derivatives have been developed and are finding their way into illegal narcotics.

“When I say fentanyl, you can extend that to newer, more potent versions of fentanyl, like carfentanil, and sufentanil, all of which are even more potent than fentanyl and can produce even greater liabilities,” he said.

How much more potent?

Carfentanil is 100 times more potent than fentanyl and 10,000 times stronger than morphine, according to the U.S. Department of Justice.

 

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