title: Aerosolized scopolamine protects against microinstillation inhalation toxicity to sarin in guinea pigs.
abstract: Sarin is a volatile nerve agent that has been used in the Tokyo subway attack. Inhalation is predicted to be the major route of exposure if sarin is used in war or terrorism. Currently available treatments are limited for effective postexposure protection against sarin under mass casualty scenario. Nasal drug delivery is a potential treatment option for mass casualty under field conditions. We evaluated the efficacy of endotracheal administration of muscarinic antagonist scopolamine, a secretion blocker which effectively crosses the blood-brain barrier for protection against sarin inhalation toxicity. Age and weight matched male Hartley guinea pigs were exposed to 677.4 mg/m³ or 846.5 mg/ m³ (1.2 × LCt₅₀) sarin by microinstillation inhalation exposure for 4 min. One minute later, the animals exposed to 846.5 mg/ m³ sarin were treated with endotracheally aerosolized scopolamine (0.25 mg/kg) and allowed to recover for 24 h for efficacy evaluation. The results showed that treatment with scopolamine increased the survival rate from 20% to 100% observed in untreated sarin-exposed animals. Behavioral symptoms of nerve agent toxicity including, convulsions and muscular tremors were reduced in sarin-exposed animals treated with scopolamine. Sarin-induced body weight loss, decreased blood O₂ saturation and pulse rate were returned to basal levels in scopolamine-treated animals. Increased bronchoalveolar lavage (BAL) cell death due to sarin exposure was returned to normal levels after treatment with scopolamine. Taken together, these data indicate that postexposure treatment with aerosolized scopolamine prevents respiratory toxicity and protects against lethal inhalation exposure to sarin in guinea pigs.
authors.affiliation: Closed Head Injury Branch, Center for Military Psychiatry and Neurosciences, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Magnus M
authors.initials: MM
authors.lastname: Che
authors.forename: Soma
authors.initials: S
authors.lastname: Chanda
authors.forename: Jian
authors.initials: J
authors.lastname: Song
authors.forename: Bhupendra P
authors.initials: BP
authors.lastname: Doctor
authors.forename: Peter E
authors.initials: PE
authors.lastname: Rezk
authors.forename: Praveena
authors.initials: P
authors.lastname: Sabnekar
authors.forename: Michael W
authors.initials: MW
authors.lastname: Perkins
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Sciuto
authors.forename: Madhusoodana P
authors.initials: MP
authors.lastname: Nambiar
mesh_terms: D000336:Aerosols; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D010100:Oxygen / Q000097:blood; D020011:Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D020545:Respiratory Mucosa / Q000187:drug effects; D012524:Sarin / Q000008:administration & dosage / Q000633:toxicity*; D012601:Scopolamine / Q000008:administration & dosage / Q000627:therapeutic use*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D016019:Survival Analysis; D014202:Tremor / Q000139:chemically induced / Q000517:prevention & control; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000336:Aerosols; D000931:Antidotes; D002619:Chemical Warfare Agents; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D020011:Protective Agents; D012524:Sarin; D012601:Scopolamine; D010100:Oxygen