Carbamate anticholinesterase agents

Carbamate anticholinesterase agents are carbamic acid esters that are hydrolyzed by AChE in a manner similar to that of ACh. Carbamates have this general structure ... 

Anticholinesterases are agents that inhibit the enzyme acetylcholinesterase (AChE) and other cholinesterases that degrade acetylcholine (ACh). The hrst known anticholinesterase agent was Calabar bean, known as ordeal poison or ordeal bean its active ingredient is the carbamate compound physostigmine (Koelle 1975). It is thought that the Calabar bean was used by native tribesmen of Western Africa who used it in witchcraft rituals. The principle behind its use was that if a tribal member was accused of a capital crime, he or she would be subjected to a trial by ordeal in which they were forced to eat Calabar beans. If a person was innocent, he or she would quickly eat the beans with little apprehension, which would quickly induce... 

Pretreatment. Carbamate anticholinesterases, e.g., pyridostigmine, may be used as pretreatments against nerve agent poisoning. For further information see Chapter 2 of FM 8-9 (Part III). 

The carbamate anticholinesterases such as PB bind reversibly with ChE enzyme, yet spontaneously reactivate relatively rapidly. However, nerve agents (organophosphate compounds) bind with the ChE irreversibly and form a much more stable phosphory-lated enzyme (ChE-OP) complex. PB binds to peripheral ChE at anionic and esteratic sites and thus carbamylates the enzyme. The carbamylated enzyme sites cannot bind with nerve agents. In the meantime, some of the nerve agents are hydrolyzed to inactive metabolites by nonspecific hydrolases. The decarbamylation of the ChE takes place at the alcohol moiety on the esteratic site, regenerating the ChE enzyme to sustain life. 

Sharma. R. P., and Tomar, R, S. (1992). Immuiiotoxicology of anticholinesterase agents. In Clinical and Experimentul Toxicology of Orgarxophospltates and Carbamates (B. Ballantyne and T. C. Marr.s, Eds.), pp. 203-210, Butterworth-Heincmann, Oxford. 

A. Actions of the nondepolarizing agents are potentiated by ether, methoxyflu-rane, and enflurane and are inhibited or reversed by anticholinesterase agents (eg, neostigmine, physostigmine, and carbamate and organophos-phate insecticides). 

Eriedman et al. have demonstrated enhanced brain penetrance under psychological stress of relatively small molecules such as anticholinesterases, as well as larger dye-protein complexes and DNA plasmids. This stress-induced process putatively explains some of the nervous system-associated sequelae reported by Gulf War veterans, who were exposed to unknown doses and combinations of potentially harmful xenobiotics, particularly anticholinesterases. The anticipated chemical warfare agents would have irreversibly blocked AChE. Eor prophylactic protection from these agents, Gulf War soldiers were administered pyridostigmine, a reversible carbamate... 

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