Carbamates pretreatment with

Gordon JJ, Leadbeater L, Maidment MP. The protection of animals against organophosphate poisoning by pretreatment with a carbamate. Toxicol. Appl. Pharmacol. 43 207-216, 1978. 

Toxicity of organophosphates can be potentiated 15-20-fold in rats and mice by pretreatment with a metabolite of tri-O-cresylphosphate, CBDP (2-0-cresyl)-4H-l,3,2-benzodioxa-phosphorin-2-oxide), which is an irreversible inhibitor of CarbEs. In similar studies, tetraisopropylpyrophosphoramide (iso-OMPA), or mipafox, an organophosphate-irreversible inhibitor of CarbEs, potentiates three-to fivefold the toxicity of several OPs (soman, DFP, and methylparathion) and carbamates (carbofuran, aldicarb, propoxur, and carbaryl). Inhibition of CarbEs by CBDP, iso-OMPA, or mipafox pretreatment, particularly in plasma, liver, heart, brain, and skeletal muscles, is a major contributory factor in the potentiation of toxicity of organophosphates and carbamates. Thus, the toxicity of any drug, pesticide, or other type of agent that is normally detoxified by CarbEs, could be potentiated by pre-exposure to an organophosphorus or other carboxylesterase inhibitor. 

Miosis, pain, dim vision, and nausea can be relieved by topical atropine in the eye. Pretreatment with carbamates may protect the cholinesterase enzymes before nerve agent exposure. 

Miosis, pain, dim vision, and nausea can be relieved by topical atropine in the eye. Pretreatment with carbamates may protect the cholinesterase enzymes before nerve agent exposure. It is available in 30 mg tablets and the tablets should be administered every 8h. When used prior to exposure, it should be followed by atropine and pralidoxime chloride after exposure. 

Anderson, D.R. et al. Effects of suhacute pretreatment with carbamate together with adjunct pretreatment against nerve agent exposure. Drug Chem. Toxicol., 14, 1, 1991. 

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. 

Harris, L.W., Heyl, W.C., Stitcher, D.L., and Moore, R.D., The effect of atropine and/or physostigmine on cerebral acetylcholine in rats poisoned with soman, LifeScL, 22,907,1978. Harris, L.W., Stitcher, D.W., and Heyl, W.C., The effects of pretreatments with carbamates, atropine and mecamylamine on survival and on soman induced alterations in rat and brain acetylcholine. Life Scl, 26, 1885, 1980. 

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