Carbamates anticholinesterase activity

Physostigma venenosum (Leguminosae/Fabaceae) and has played an important role in pharmacology because of its anticholinesterase activity. The inherent activity is in fact derived from the carbamate side-chain rather than the heterocyclic ring system, and this has led to a range of synthetic materials being developed. 

Once the medicinal properties of I and II were appreciated, the inevitable synthesis of carbamate analogs followed. The anticholinesterase activity of physostigmine- and eserine-related synthetics suggested their possible use as Insecticides but tests of early compounds failed, due to the quaternary ammonium barrier to penetration of the insect cuticle present in them. 

The multiplicity of abiotic transformation products which have been detected for aminocarb has prompted a comparison of the anticholinesterase activity, in vivo insect toxicity and relative volatility of a series of oxidation products. Successive oxidations of the aryldimethylamino group resulted in increased toxicity whereas oxidation of the arylmethyl group or of the carbamate N-methyl group considerably reduced toxicity. Saturated vapour concentrations of the toxic transformation products were only slightly lower than the parent carbamate. 

Brufani M, Marta M, Pomponi M. Anticholinesterase activity of a new carbamate, heptylphysostigmine, in view of its use in patients with Alzheimer-type dementia. Eur.J. Biochem., 986,... 

Maxwell, D.M., Lenz, D.E. (1992). Structure-activity relationships and anticholinesterase activity. In Clinical and Experimental Toxicology of Organophosphates and Carbamates (B. Ballantyne, T.C. Marrs, eds), pp. 47-58. Butterworth-Heinemann, Oxford. 

Jones and co-workers used regression analyses to study the effects of field constants and resonance parameters (110) of some carbamate derivatives on their penetration and detoxication with some success (111). Similar studies have also been made by Fukuto and co-workers using selected oximes and their anticholinesterase activities (112). Kakeya et al. used chemical shifts and valence force constants in addition to other thermodynamic parameters in the structure-activity study of a series of sulfonamide carbonic anhydrase inhibitors (113). 

Carbachol (see structure above), the carbamate analogue of acetylcholine, shows no selectivity for muscarinic or nicotinic receptors. Because it is a carbamate ester, carbachol is more resistant toward acid-, base-, or enzyme (AChE)-catalyzed hydrolysis than acetylcholine. It also is reported to exhibit weak anticholinesterase activity. Both of these actions work to prolong the duration of action of carbachol. Because of erratic absorption and its actions at nicotinic receptors, use of carbachol has been limited to the treatment of glaucoma and for the induction of miosis in ocular surgery. Carbachol is available as an intraocular solution and an ophthalmic solution. 

This assay is not intended to yield the identities or exact concentrations of the carbamate and OP insecticides present, but rather the relative anticholinesterase activity. More specifically, this screening assay is intended to flag samples which, from a potential risk perspective, warrant further examination for specific carbamate and organophosphorus insecticide contamination. In this respect, the assay performed exceptionally well using standards in laboratory buffers. Although the assay underestimated the inhibition expected from laboratory standards, the AChE-based assay detected anticholinesterase activity present in all of the environmental samples. 

Carbamates - Structure activity relationships have been studied with respect to toxicity and anticholinesterase activity. 9 The mechanism of acetylcholinesterase inhibition by the carbamates is not entirely clear. 

The major action resulting from human exposure to diazinon is the inhibition of cholinesterase activity (refer to Section 2.4 for discussion). Two pools of cholinesterases are present in human blood acetylcholinesterase in erythrocytes and serum cholinesterase (sometimes referred to as pseudocholinesterase or butyrlcholinesterase) in plasma. Acetylcholinesterase, present in human erythrocytes, is identical to the enzyme present in neural tissue (the target of diazinon action) while serum cholinesterase has no known physiological function. Inhibition of both forms of cholinesterase have been associated with exposure to diazinon in humans and animals (Coye et al. 1987 Edson and Noakes 1960 Soliman et al. 1982). Inhibition of erythrocyte, serum, or whole blood cholinesterase may be used as a marker of exposure to diazinon. However, cholinesterase inhibition is a common action of anticholinesterase compounds such as organophosphates (which include diazinon) and carbamates. In addition, a wide variation in normal cholinesterase values exists in the general population, and there are no studies which report a quantitative... 

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... 

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