Two medical therapies very effective shortly after high levels of soman poisoning in rats, but only one with universal utility

Author
Myhrer, Trond
Enger, Siri
Mariussen, Espen
Aas, Pål
Date Issued
2013
Keywords
Soman
Forgiftning
Rotter
Permalink
http://publications.ffi.no/handle/123456789/453
DOI
10.1016/j.tox.2013.08.005
Collection
Articles
Description
Myhrer, Trond; Enger, Siri; Mariussen, Espen; Aas, Pål. Two medical therapies very effective shortly after high levels of soman poisoning in rats, but only one with universal utility. Toxicology 2013 ;Volum 314.(2-3) s. 221-228
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Abstract
A treatment regimen consisting of HI-6, scopolamine, and physostigmine (termed the physostigmine regimen) has been based on the serendipitous discovery that it exerts powerful antidotal effects against high levels of soman poisoning if it is administered 1 min after exposure. A medical therapy with corresponding efficacy, but without the time limitation of the latter regimen, has been developed through studies of microinfusions of anticonvulsants into seizure controlling sites in the forebrain of rats. From these studies procyclidine emerged as the most potent anticonvulsant, and its potency was further enhanced when being combined with the antiepileptic levetiracetam during systemic administration. In the present study, the capacity of HI-6, levetiracetam, and procyclidine (termed the procyclidine regimen) was tested against that of the physostigmine regimen. The results showed that both regimens were very effective against supralethal doses of soman (3, 4, 5 × LD50) when given 1 and 5 min after intoxication. When the treatments were administered 10 and 14 or 20 and 24 min after soman exposure, only the procyclidine regimen was able to terminate seizures and preserve lives. When used as prophylactic therapies, both regimens protected equally well against seizures, but only the procyclidine regimen provided neuroprotection. The procyclidine regimen has apparently capacities to serve as a universal therapy against soman intoxication in rats.
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