Organophosphorus compounds nervous system

Among the irreversible inhibitors are organophosphorus compounds, which inhibit the enzyme acetylcholinesterase and similar enzymes. Organophosphorous compounds include nerve gases (such as sarin), that work on the human nervous system, and insecticides like malathion. 

Plasma or serum cholinesterase (pseudocholinesterase) is inhibited by a munber of compounds and can also be decreased in ftie presence of liver impairment. Erythrocyte cholinesterase (true cholinesterase) reflects more accurately the cholinesterase status of the central nervous system. However, pseudocholinesterase activity responds more quickly to an inhibitor and returns to normal more rapidly than eiythrocyte-cholinesterase activity. Thus, measurement of pseudocholinesterase activity is quite adequate as a means of diagnosing acute exposure to organophosphorus compounds, but cases of illness which may be due to chronic exposure to these compounds should also be investigated by determining the erydirocyte-cholinesterase activity. A colorimetric method for this purpose has been reported (K.-B. Augustinsson et ah, Clinica chim. Acta, 1978, 89, 239-252). 

Lemercier, G., Carpentier, P., Sentenac-Roumanou, H., Morelis, P. (1983). Histological and histochemical changes in the central nervous system of the rat poisoned by an irreversible anticholinesterase organophosphorus compound. Acta Neuro-pathol. 61 123-9. 

The term delayed neurotoxicity may be used to describe any type of toxicity to the nervous system involving a delay between the precipitating chemical exposure and the appearance of neurological signs or symptoms. However, this designation usually refers to organophosphorus (OP) compound-induced delayed neurotoxicity (or delayed neuropathy) (OPIDN), also known as OP compound-induced delayed polyneuropathy (OPIDP). 

Randall, J.C., Yano, B.L., and Richardson, R. J., Potentiation of organophosphorus compound-induced delayed neurotoxicity (OPIDN) in the central and peripheral nervous system of the adult hen distribution of axonal lesions, J. Toxicol. Environ. Health., 51(6), 571-590,1997. 

Chemicals which can damage (a) the liver, include carbon tetrachloride, paracetamol, bromobenzene, isoniazid, vinyl chloride, ethionine, galactosamine, halothane, dimethylnitrosamine (b) the kidney, include hexachlorobutadiene, cadmium and mercuric salts, chloroform, ethylene glycol, aminoglycosides, phenacetin (c) the lung, include paraquat, ipomeanol, asbestos, monocrotaline, sulphur dioxide, ozone, naphthalene (d) the nervous system, include MPTP, hexane, organophosphorus compounds, 6-hydroxydopamine, isoniazid (e) the testes, include cadmium, cyclophosphamide, phthalates, ethanemethane sulphonate, 1,3-dinitrobenzene (f) the heart, include allylamine, adriamycin, cobalt, hydralazine, carbon disulphide (g) the blood, include nitrobenzene, aniline, phenylhydrazine, dapsone. 

The further classification of conventional insecticides, acting chiefly on the insect nervous system, is a chemical one compounds of natural origin, arsenic compounds, chlorinated hydrocarbons, organophosphorus compounds, carbamates, and other compounds. 

Butyrylcholinesterase occurs in the liver and at the motor endplates in muscle fibers and at synapses together with aeetylcholinesterase (Silver 1974). It is estimated that approximately 15% of total cholinesterase activity in the nervous system is due to the nonspecific cholinesterase activity in some of the white matter (Ecobichon and Joy 1982), and the synthesis of this nonspecific cholinesterase occurs in the liver. Several organophosphorus compounds can react and phosphorylate acetylcholinesterase carbamate ester compounds can carbamylate the enzyme, so both can inhibit the acetylcholinesterase. 

The nerve gases are powerful inhibitors of the enzyme acetylcholinesterase (AChE), which causes rapid hydrolysis of acetylcholine. They are also inhibitors of butyryl-choUnesterase and carboxylesterase. Acetylcholine is the chemical that is released to transmit nerve impulses in the central nervous system and also at several peripheral locations. Once the impulse is transmitted, acetylcholine must be removed instantaneously for proper functioning of the nervous system. Such removal is done by the enzyme AChE, which is found extensively in nervous system and many non-nervous tissues. Nerve gases and other organophosphorus compounds bind... 

G-series nerve agents. This series of iionpersistent nerve agents includes tabun. sarin, soman, and GF. They are organophosphorus compounds that inhibit action of a key nervous system enzyme (acetylcholinesterase). 

A. Organophosphorus (OP) compounds inhibit the enzyme acetylcholinesterase (AChE), allowing the accumulation of excessive acetylcholine at muscarinic receptors (cholinergic effector cells), at nicotinic receptors (skeletal neuromuscular junctions and autonomic ganglia), and in the central nervous system. 

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