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Toxicological Sciences 53, 84-91 (2000)
Copyright © 2000 by the Society of Toxicology

Subchronic Physostigmine Pretreatment in Marmosets: Absence of Side Effects and Effectiveness against Soman Poisoning with Negligible Postintoxication Incapacitation

I. H. C. H. M. Philippens*,1, R. A. P. Vanwersch*, B. Groen*, B. Olivier{dagger}, P. L. B. Bruijnzeel* and B. P. C. Melchers*

* Department of Pharmacology, TNO Prins Maurits Lab (TNO-PML), P.O. Box 45, 2280 AA Rijswijk ZH, The Netherlands; {dagger} Department of Psychopharmacology, Rudolf Magnus Institute for Neurosciences, Faculty of Pharmacy, Utrecht University, Utrecht, The Netherlands

Subchronic pretreatment with physostigmine (PHY) (0.0125 mg/kg/h) leading to a blood acetylcholinesterase inhibition of about 30% caused no side effects when applied to marmoset monkeys. This was evident on behavioral parameters and on EEG and cortical visual evoked response. Furthermore, this treatment regime, followed by atropine as postintoxication therapy, protected the marmosets against lethality after a 2 x LD50 dose of soman with negligible postintoxication incapacitation. These findings suggest that a symptom-free pretreatment with subchronic PHY could protect man sufficiently against severe soman intoxication.

Key Words: organophosphate; physostigmine; soman; AChE; ACh; marmoset monkeys.


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