Intranasal Formulations for Organophosphorus Nerve Agent Poisoning: A Review of Recent Developments in Treatment and Prophylaxis

Organophosphorus (OP) nerve agents represent a grave global threat, encompassing both chemical warfare agents and highly toxic pesticides. The high morbidity and mortality associated with OP exposure, primarily due to the irreversible inhibition of acetylcholinesterase (AChE), underscore the critical need for rapid and effective medical countermeasures. Current standard-of-care, which relies on intramuscular or intravenous administration of anticholinergics (atropine) and cholinesterase reactivators (oximes), is limited by logistical challenges and, crucially, an inability to provide adequate protection to the central nervous system (CNS). This review examines the burgeoning field of intranasal (IN) formulations as a novel paradigm for OP antidote delivery. The IN route offers a direct nose-to-brain pathway that bypasses the restrictive blood-brain barrier (BBB), enabling CNS-targeted therapy. Preclinical research has demonstrated that IN obidoxime can completely prevent mortality and seizure-induced neuronal degeneration in animal models, an effect not observed with standard peripheral treatment. The clinical success of intranasal diazepam for seizure control provides a powerful precedent for this approach. Moreover, IN delivery holds promise for the rapid administration of prophylactic agents and next-generation bioscavengers. While the absence of human clinical trials for IN nerve agent antidotes remains a significant research gap, the well-documented advantages and efficacy of intranasal naloxone in a similar emergency setting provide a strong rationale for continued development. This report synthesizes recent findings, analyzes the comparative advantages of IN formulations, and identifies key research directions to translate these promising countermeasures into clinical practice.

کلیدواژه ها:

Organophosphorus Poisoning: Nerve Agent Antidotes ، Prophylaxis ، Intranasal Delivery ، Nose-to-Brain Pathway ، Blood-Brain Barrier