Prophylaxis against organophosphate poisoning by sustained release of scopolamine and physostigmine

Journal of Applied Toxicology : JAT
Y MeshulamA Levy

Abstract

Protection efficacy of continuous prophylactic administration of physostigmine and scopolamine against sarin-induced toxicity was evaluated previously in guinea pigs. The present study in large animals used Beagle dogs, that serve as an animal model with cholinergic sensitivity similar to that of humans. Pretreatment with physostigmine salicylate and scopolamine hydrochloride at dose rates of 2.5 and 1 microg x kg(-1) x h(-1), respectively, was administered via Alzet mini-osmotic pumps. At the time of exposure, the physostigmine salicylate concentration in plasma was 0.7 ng x ml(-1) and the scopolamine hydrochloride concentration was ca. 0.2 ng x ml(-1), both of which are levels known to be well tolerated in humans. Whole-blood cholinesterase inhibition was 15-20%. This regimen conferred full protection against 2.5 x LD50 i.v. of sarin. Albeit the high-dose exposure, cholinergic toxicity symptoms were mild with no convulsions. About 11-14 min following poisoning the treated animals started to walk and 15-20 min following exposure full recovery was observed and the dogs behaved normally. With higher dose rates of physostigmine salicylate and scopolamine hydrochloride, at plasma concentrations of 2.1 and 0.6 ng x ml(-1), respecti...Continue Reading

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Citations

Mar 18, 2009·Journal of Veterinary Pharmacology and Therapeutics·M R BonhageW S Flournoy
Oct 13, 2006·Toxicology·Murray G Hamilton, Paul M Lundy
Oct 25, 2016·Neuroscience and Biobehavioral Reviews·Trond Myhrer, Pål Aas
Mar 5, 2019·Mini Reviews in Medicinal Chemistry·J BajgarK Kuca

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