Carbamates anti-ChEs

The CBs used as pesticides are N-substituted esters of carbamic acid. CBs developed in the 1950s as insect repellents were found to have insecticidal activity, leading to the development of the napthyl CBs with high anti-ChE activity and selective toxicity against insects. One example is carbaryl it is widely used because of its low toxicity to mammals and its degradability. Aldicarb, a plant systemic, is more toxic than carbaryl. A few years ago aldicarb was associated with a July 4th holiday incident when West Coast residents complained of anticholinergic symptoms after eating aldicarb-contaminated watermelon. 

Human subjects may be exposed to carbamate (CM) or organophosphate (OP) anticholinesterases (anti-ChEs) topically and/or systemically as a consequence of the wide range of their uses, which may result in exposures from deliberate, incidental, or accidental situations. These uses include the following ... 

Plant-originated anti-ChEs, such as huperzine A, have been used for thousands of years in the treatment of aging-induced memory impairment (Haviv et al., 2007). In 1877, prior to the discovery of ACh as a neurotransmitter in the brain, physostigmine (eserine)— a carbamate extracted from the seeds of Physostigma venenosum—became the first cholinesterase inhibitor used therapeutically to control increased ocular pressure caused by wide-angle glaucoma (Taylor, 1996). 

Cholinesterase inhibitor (anti-cholinesterase, ChEI) is a chemical that prevents cholinesterases (ChEs) from breaking down. ACh, which consequently increases the level and duration of action of this neurotransmitter. ChEIs such as organophosphates (esters of phosphoric acid) and carbamates (esters of carbamic acid) - serve as insecticides, pesticides, warfare agents and drugs. 

Based on features of their interaction with ChE, anti-cholinesterase substances are clas-sified as reversible and irreversible inhibitors. Referred to the reversible anti-cholinesterase substances are quaternary ammonium compounds and aminoformic acid esters OPC are referred to the irreversible anti-cholinest-erase substances. At the same time, a great amount of anti-cholinesterase substances, carbamates in particular, though induce transitional reversible inhibition of ChE, are irreversible reagents. They are destroyed on the enzyme surface. 

Derivatives of aminoformic acid react with ChE similarly to OPC, i.e. in two stages with establishing a covalent bond. A degree of the anti-cholinesterase action of carbamates depends upon strength of the complexes formed. Evidently, the phosphorylated ChE becomes disabled for a more prolonged period, as compared with the carbamylated ChE. Rapidity of the initial activity restoration of the enzyme inhibited by carbamates is determined, respectively, by the carbamylated enzyme hydrolysis speed, which depends upon the inhibitor structure. Carbamy-... 

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