Novel Medical Countermeasures for Opioid Intoxication

Synthetic opioids including fentanyl and its derivatives pose a serious threat to both civilians and warfighters. The serum half-life of the current FDA-approved antidote for acute opioid poisoning, naloxone, is shorter than that for fentanyl and its synthetic analogs, and thus does not provide effective protection against these threat agents. The mechanism of action of naloxone is by competitive antagonism at μ-opioid receptors in the central and peripheral nerve systems. Not surprisingly, renarcotization is known to occur as the effect of naloxone dissipates, as fentanyl(s) clearance from the body is relatively slow, and multiple doses of naloxone are often required. We propose to develop a novel class of medical countermeasures that address the drawbacks of naloxone via a different mechanism of action, thus providing improved treatment for both immediate rescue and prolonged protection without renarcotization. The novel medical countermeasure will also allow the use of current opioid-based protocols for pain management.