Physostigmine pretreatment

Philippens IHCHM, Busker RW, Wolthuis OL, Olivier B, Bruijnzeel PLB, Melchers BPC. Subchronic physostigmine pretreatment in guinea pigs effective against soman and without side effects. Pharmacol. Biochem. Behav. 59(4) 1061-1067, 1998. 

Anderson DR, Harris LW, Lennox WJ (1989) Subacute vs. acute physostigmine pretreatment against soman poisoning. USAMRDC Med Def Biocsi Rev, pp 511-514. (Cited in Somani et al. 1992.)... 

Keywords behaviour guinea pig physostigmine, procyclidine pretreatment ... 

Philippens IHCHM, Groen B, Vanwersch RAP. Direct effects of physostigmine as a pretreatment in guinea pigs side effects and efficacy against soman. Proc.TG004 meeting, Medicine Hat, Canada, 2003. 

A third approach to protection against excessive AChE inhibition lies in pretreatment with reversible inhibitors of the enzyme to prevent binding of the irreversible organophosphate inhibitor. This prophylaxis can be achieved with pyridostigmine or physostigmine but is reserved for situations in which possibly lethal poisoning is anticipated, eg, chemical warfare. Simultaneous use of atropine is required to control muscarinic excess. 

Jenner J, Saleem A, Swanston D. Transdermal delivery of physostigmine. A pretreatment against organophosphate poisoning./. Pharm. Pharmacol., 1995, 47(3), 206-212. 

Muggleton, N.G., Bowditch, A.P., Crofts, H.S., Scott, E.A.M., Pearce, P.C. (2003). Assessment of a combination of physostigmine and scopolamine as pretreatment against the behavioural effects of organophosphates in the common marmoset (Callithrix jacchus). Psychopharmacology 166 212-20. 

Tuovinen, K., Harminen, O. (1999). Protection of mice against soman by pretreatment with eptastigmine and physostigmine. Toxicology 139 233 1. 

Deshpande, S.S. et al. Effectiveness of physostigmine as a pretreatment drug for protection of rats from organophosphate poisoning, Fundam. Appl. Toxicol., 6, 566, 1986. 

Harris, L.W. et al. Physostigmine (alone and together with adjunct) pretreatment against soman, sarin, tabun and VX intoxication. Drug Chem. Toxicol, 14, 265, 1991. 

Miller, S.A. et al. Efficacy of physostigmine as a pretreatment for organophosphate poisoning, Pharmacol. Biochem. Behav., 44, 343, 1993. 

The concept of using carbamates as pretreatment which protects against OP intoxication was first mooted in 1956 by Koster who demonstrated that cats pretreated with a small dose of eserine (physostigmine) survived poisoning by supralethal doses of diisopropylphosphorofluori-date (DFP) (Koster, 1956). Subsequently, Berry and Davies (1970) demonstrated the effectiveness of a combination of atropine and carbamate pretreatment against soman poisoning. At that time, it was not considered that pretreatments with substances such as atropine, with marked actions on the central nervous system, would be acceptable for human use. For this reason, effort was concentrated upon pretreatment with pyridostigmine, a quaternary carbamate, which would not be expected to cross the blood-brain barrier and affect the central nervous system. 

FUTURE PROSPECTS PRETREATMENT WITH PHYSOSTIGMINE AND HYOSCINE... 

More recently, as mentioned above, effort has been focused on the development of an alternative pretreatment based upon the centrally acting carbamate physostigmine, which has continued to be of interest despite having previously been considered and discounted because of concerns about its potential side-effects and relatively narrow therapeutic window. These concerns have largely been addressed by the concept of coadministration of the potent muscarinic antagonist, hyoscine, which has been shown to reduce... 

Figure 2. Duration of loss of posture and performance of a visually guided reaching task in marmosets pretreated with pyridostigmine or physostigmine/hyoscine, and challenged with (a) sarin or (b) soman.

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