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Vaccine Developed to Stop Synthetic Opioids

Fentanyl patch products

Fentanyl patch products (Alcibiades, Wikimedia Commons)

17 February 2016. Fentanyl is a synthetic opioid drug for treating severe pain after surgery, and in some cases chronic pain, but is also highly addictive and increasingly abused, with growing numbers of overdose deaths. Researchers from Scripps Research Institute in La Jolla, California developed a vaccine that in lab mice prevents ingredients in fentanyl from reaching the brain, as reported in yesterday’s (16 February) issue of the journal Angewandte Chemie (paid subscription required).

Like other opioids, fentanyl binds to receptors in the brain that control pain, but also emotions, and drives up dopamine levels in these brain regions. Fentanyl alone given as an injection or patch is considered a powerful opioid pain killer — up to 500 times more powerful than morphine — but can become addictive. When mixed with street drugs, like heroin, the drug’s effects are amplified leading to sedation, unconsciousness, and coma, and sometimes death.

In some cases, street versions of fentanyl are so potent, even casual exposure is considered dangerous. In March 2015, the U.S. Drug Enforcement Agency issued an alert for law enforcement on inhaling or making physical contact with some fentanyl derivatives during drug arrests.

The team from the lab of Scripps biochemist Kim Janda devised a vaccine that generates antibodies to block fentanyl’s effects. Janda’s lab investigates immunotherapy approaches to addiction, including synthesis of small hapten molecules that generate an immune response when combined with larger proteins to attack the target.

The authors say their vaccine creates high antibody levels that address a range of different fentanyl compounds. In lab tests, the team gave mice three injections of the vaccine every two weeks, then tested various levels of fentanyl in the mice. Results of blood tests, with an optical analysis technique measuring protein binding, show the vaccine created antibodies that neutralized fentanyl in the mice.

Only at levels 30 times the normal dose of fentanyl did the researchers find neural circuits in the brains of mice activated by the drug. Antibodies produced by the vaccine say the authors, also stopped overdoses from lethal levels of fentanyl.

While the vaccine protects against against a wide range of fentanyl derivatives, it does not inhibit other types opioids, such as oxycodone. As a result, say the researchers, individuals needing opioids as legitimate pain killers could continue taking those drugs.

The team next plans to design a vaccine that addresses combinations of fentanyl and heroin. “We want to stay one step ahead of these clandestine laboratories making illegal opioids for black market demand,” says Janda in a Scripps statement. “The importance of this new vaccine is that it can block the toxic effects of this drug, a first in the field.”

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