Organophosphorus compounds central nervous system

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 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... 

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. 

At around the same time, a small circle of Nazi officials learned about the discovery of Soman, one of the most deadly nerve agents known to man, which stiU required further development. Unbeknown to Schrader and many others working in the chemical warfare field, Richard Kuhn, director of the Kaiser Wilhelm Institute for Medical Research in Heidelberg, and his team of scientists had been commissioned by the military to screen various organophosphorus compounds for their level of cholinesterase (ChE) inhibition, and had discovered Soman in the process. When inhaled. Soman turned out to be twice as toxic as Sarin, was able to penetrate through the skin, and quickly affected the central nervous system. Because it inhibited cholinesterase very rapidly, the effective use of antidotes such as atropine was considerably reduced. Experiments on dogs and apes at Gross laboratory in Elberfeld quickly established the enormous toxicity of the new substance. 

The inhibition of AChE leads to the accumulation of the neurotransmitter ACh in synapses of the central and peripheral nervous systems and over-stimulation of post-synaptic cholinergic receptors. Exposure to even small amounts of an organophosphorus compound can be fatal as the poison causes seizures, convulsions and lesions of the central nervous system. The current standard treatment for poisoning usually consists of combined administration of anticholinergic drugs (preferably atropine) and AChE reactivators (called oximes). 

It is known that human exposure to organophosphorus compounds can result in a variety of acute toxic effects. These arise primarily as a result of the inhibition of acetylcholinesterase. Signs of acute toxicity are due to effects on the central nervous system (anxiety, ataxia, hypotension), to muscarinic effects (wheezing, cough, rhinitis) and to nicotinic effects (muscle weakness, mydriasis and tachycardia). Other acute effects include chest tightness, abdominal cramps, confusion and convulsions. With some organophosphorus compounds, a specific syndrome may develop. This is delayed peripheral neuropathy or OP-induced delayed neuropathy (OPIDN). (For a more detailed discussion on the toxicity of organophosphorus compounds see Chapter 10.)... 

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. 

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