Nerve agent antidotes
Although they were banned in 1997, chemical weapon nerve agents continue to pose a threat to warfighters and civilians. Existing antidotes administered following exposure reverse the nerve agent’s effect on the peripheral nervous system, but they cannot penetrate the blood–brain barrier (BBB) and protect the central nervous system, which controls critical processes such as respiration.
In response to this challenge, scientists at LLNL developed a new, versatile antidote to counteract exposure to nerve agent poisoning. After identifying the most promising compounds through computational modeling, they analyzed candidates using the Lab’s bioAMS capabilities. They measured the movement of radio-labeled versions of the compounds in biological systems, enabling them to quantify how much of the compound was able to penetrate the BBB, and how quickly it reached the brain. The experimental data helped researchers validate computer simulations. As a result of these efforts, they discovered that a compound known as LLNL-02 that can penetrate the BBB and protect the brain against the effects of nerve agents.
LLNL is one of a handful of U.S. institutions, including the Army, that is cleared to use actual nerve agents for these types of evaluations.
Key collaborator: U.S. Army Medical Research Institute of Chemical Defense
What’s next: During follow-on studies, researchers will assess the ability of LLNL-02 to protect against nerve agent exposure and determine the toxicity of the compound under various scenarios. These studies will help determine if LLNL-02 is safe and effective and could possibly move forward for FDA approval.
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Treating fentanyl overdoses
LLNL researchers discovered a promising new treatment to counteract the effects of fentanyl and related synthetic opioids. The compound they identified as an effective fentanyl treatment, known as subetadex-α-methyl (SBX-Me), was first developed in 2002, but it had not previously been tested against fentanyl until LLNL researchers explored this option.
They discovered that SBX-Me remains active in the body for approximately seven hours (far longer than existing drugs used to treat fentanyl overdoses). In addition, it encapsulates the opioid, preventing it from binding to opioid receptors in the body and speeding up its clearance from the affected individual. As such, it significantly reduces recovery times.
Scientists conducted a pharmacokinetic study of SBX-Me, using LLNL’s bioAMS instrument to analyze the movement of a carbon-radiolabeled version of the compound. They were able to quantify the levels of SBX-Me in each tissue with extreme sensitivity and precision. Findings showed favorable pharmacokinetics in the blood and a rapid clearance of SBX-Me from major organs, such as the heart, liver, brain and kidney.
What’s next: The research team hopes to increase the half-life of SBX-Me so it can be used prophylactically or as a preventative measure for first responders or the military. They are also exploring whether they can expand the range of the drug as a broad-spectrum treatment against other opioids.
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