Anticholinesterase

There is some confusion in the literature regarding the sub-stances designated as anti-choline esterases (usually shortened to anticholinesterases). The term chohnesterase was first used in connexion with an enzyme present in the blood serum of the horse which catalysed the hydrolysis of acetylcholine and of butyrylchohne, but exhibited httle activity towards methyl butyrate, 

We may now consider in a httle more detail the interaction of true (or a ) cholinesterase with acetylcholine. Wilson and Berg-mann suggest that there are two active sites in the enzyme, known as anionic site and esteratic site respectively. These sites (represented diagrammatically in fig. 11) are not to be con-sidered independent. The mode of attachment will be seen to 

Depending upon the part of the enzyme with which the anti-cholinesterases react, the latter can be readily classified. In the first place there are a few compounds (e.g. mercuric chloride) that combine with the enzyme at sites other than those men-tioned, thus providing a type of inhibition which is non-competitive with the substrate. The vast majority of inhibi tions, however, compete with the substrate for positions on the enzyme. Depending upon the point of attachment, competitive inhibitors have been classified thus 

It may be noted that many of the antichohnesterases of the competitive type are equally potent as inhibitors of a- and yff-cholinesterases. We should add, however, that the existence of an anionic site in / -cholinesterases has been questioned.  

To test this possibility, they first examined the effect of phosphorofluoridates on isolated rabbit s intestine. On such a preparation the action of drugs, like acetylcholine, which act directly on the muscle differs characteristically from the action of those, like eserine, which act by inhibition of cholinesterase activity. The directly acting drugs produce an immediate contraction which proceeds rapidly to a maximum, and after the drug has been washed out the muscle again quickly relaxes. The contraction produced by cholinesterase-inhibiting drugs, such as 

Several modifications, including the use of dual electrode coulometric detection, a high speed reciprocating pump and the A,A-dimethyl analogue of physostigmine as the internal standard, decreased the LoD to 25ngL (RSD=19.6%, 4mL 

Post-column hydrolysis of carbamate esters, such as carbaryl, was discussed in Chapter 4, Section 2. Further consideration of anticholinesterase insecticides can be found in Chapter 7, Section 4. 

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The alkyl and alkoxy substituents of phosphate or phosphonate esters also affect the phosphorylating abiUty of the compound through steric and inductive effects. A satisfactory correlation has been developed between the quantitative measure of these effects, Tafts s O, and anticholinesterase activity as well as toxicity (33). Thus long-chain and highly branched alkyl and alkoxy groups attached to phosphoms promote high stabiUty and low biological activity. 

Dialkylphosphorochloridates, (R0)2P(=0)C1, react with trialkyl phosphate esters to give organic pyrophosphates. Organopyrophosphates are anticholinesterase agents and should be handled with great caution (16). Atropine sulfate is a specific antidote. 

A. Goodman and H. Martens, Studies on the Use of Ulectric Tel Acetylcholinesterasefor Anticholinesterase Agent Detection, Edgewood Arsenal Report No. 

Biosensors ai e widely used to the detection of hazardous contaminants in foodstuffs, soil and fresh waters. Due to high sensitivity, simple design, low cost and real-time measurement mode biosensors ai e considered as an alternative to conventional analytical techniques, e.g. GC or HPLC. Although the sensitivity and selectivity of contaminant detection is mainly determined by a biological component, i.e. enzyme or antibodies, the biosensor performance can be efficiently controlled by the optimization of its assembly and working conditions. In this report, the prospects to the improvement of pesticide detection with cholinesterase sensors based on modified screen-printed electrodes are summarized. The following opportunities for the controlled improvement of analytical characteristics of anticholinesterase pesticides ai e discussed ... 

Taylor P (1990) Anticholinesterase agents. In Gilman AG, Rail TW, Nies AS, Taylor P (eds) The pharmacological basis of therapeutics. Pergamon Press, New York, pp 131-149... 

When amphotericin B or diuretics are administered with ACTH, the potential for hypokalemia is increased. There may be an increased need for insulin or oral antidiabetic drag s in the patient with diabetes who is taking ACTH. There is a decreased effect of ACTH when the agent is administered with the barbiturates. Profound muscular depression is possible when ACTH is administered with the anticholinesterase drugp. Live virus vaccines taken while taking ACTH may potentiate virus replication, increase vaccine adverse reaction, and decrease the patient s antibody response to the vaccine... 

Use antidote (against anticholinesterase-alkylphosphate), cholinesterase reactivator... 

Relative contraindications to the use of anticholinesterase treatment include a history of cardiovascular disease, asthma, glaucoma, and gastrointestinal or genitourinary obstruction. Symptomatic treatment of tachyarrhythmias with propranolol may be considered P blockers, however, are less effective than physostigmine. 

Individuals with hereditary low plasma cholinesterase levels (Kalow 1956 Lehman and Ryan 1956) and those with paroxysmal nocturnal hemoglobinuria, which is related to abnormally low levels of erythrocyte acetylcholinesterase (Auditore and Hartmann 1959), would have increased susceptibility to the effects of anticholinesterase agents such as methyl parathion. Repeated measurements of plasma cholinesterase activity (in the absence of organophosphate exposure) can be used to identify individuals with genetically determined low plasma cholinesterase. 

Benke GM, Cheever KL, Mirer FE, et al. 1974. Comparative toxicity, anticholinesterase action and metabolism of methyl parathion and parathion in sunfish and mice. Toxicol Appl Pharmacol 28 97-109. 

Bhattacharya S. 1993. Target and non-target effects of anticholinesterase pesticides in fish. Sci Total Environ Supp. 1993 859-866. 

Bowers MB Jr, Goodman E, Sim VM. 1964. Some behavioral changes in man following anticholinesterase administration. J Nerv Ment Bis 138 383-389. 

Costa LG, Schwab BW, Murphy SD. 1982. Tolerance to anticholinesterase compounds in mammals. Toxicology 25 79-97. 

Galal EE, Latif MA, Kandil A, et al. 1975. The percutaneous cardiac toxicokinesis of anticholinesterase insecticides. J Drug Res 7 29-43. 

Galal EE, Samaan HA, Nour El Dien S, et al. 1977. Studies on the acute and subchronic toxicities of some commonly used anticholinesterase insecticides in rats. J Drug Res Eg t 1-17. 

Gordon CJ. 1994. Thermoregulation in laboratory mammals and humans exposed to anticholinesterase agents. Neurotoxicol Teratol 16 427-453. 

Grob D, Garlick WL, Harvey AM. 1950. The toxic effects in man of the anticholinesterase insecticide parathion (p-nitrophenyl diethylthionophosphate). Johns Hopkins Med J 87 106-129. 

Gupta RC, Goad JT, Kadel WL. 1996. Distribution and responses of brain biomarkers to anticholinesterase insecticides exposure. FASEB J 10 A690. 

Johns RJ, McQuillen MP. 1966. Syndrome simulating myasthenia gravis Asthenia with anticholinesterase tolerance. Ann NY Acad Sci 135 385-397. 

Murphy SD, DuBois KP. 1958. The influence of various factors on the enzymatic conversion of organic thiophosphates to anticholinesterase agents. J Pharmacol Exp 124 194-202. 

Rider JA, Moeller HC. 1964. Studies on the anticholinesterase effects of systox and methyl parathion in humans [Abstract], Fed Proc 23 176. 

Rider JA, Puletti EJ. 1969. Studies on the anticholinesterase effects of gardona, methyl parathion, and guthion in human subjects. Fed Proc 28 479. 

Rider JA, Swader Jl, Puletti EJ. 1970. Methyl parathion and guthion anticholinesterase effects in human subjects [Abstract]. Fed Proc 29 349. 

Schwab BW, Murphy SD. 1981. Induction of anticholinesterase tolerance in rats with doses of disulfoton that produce no cholinergic signs. J Toxicol Environ Health 8 199-204. 

Senanayake N, Karalliedde E. 1992. Intermediate syndrome in anticholinesterase neurotoxicity. In Ballantyne B, Marrs TC, ed. Clinical and experimental toxicology of organophosphates and carbamates. Jordan Hill, Oxford, England Butterworth-Heinemann Etd., 57-62. 

Taylor P. 1985. Anticholinesterase agents. Chapter 6. In Gilman AG, Goodman LS, Rail TW, et al., eds. Goodman and Gilman s the pharmacological basis of therapeutics. 7th ed.. New York, NY MacMillan Publishing Co. 110-129. ... 

Physostigmine (eserine) is a carbamate found in the calabar bean (Physostigma benenosum), which acts as an anticholinesterase. It was used in West Africa in witchcraft trials by ordeal. It has also been used in human medicine. Insecticidal carbamates are structurally related to it and also act as anticholinesterases (Ballantyne and Marrs 1992). 

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