Nervous system organophosphorus

Hahn T, Ruhnke M, Luppa H. 1991. Inhibition of acetylcholinesterase and butyrylcholinesterase by the organophosphorus insecticide methyl parathion in the central nervous system of the golden hamster i Mesocricetus aumtus). Acta Histochem (Jena) 91 13-19. 

Azinphos-methyl is unstable in basic conditions and can degrade to benzazimide, hydroxymethyl-benzazimide, mercaptomethylbenzazimide or bis(benzazimide-A/-methyl) sulfide Azinphos-methyl is an organophosphorus insecticide used to control chewing and sucking mites and insects such as aphids and scale. Azinphos-methyl has both contact and stomach action. Azinphos-methyl is a cholinesterase inhibitor and interferes with the nervous system... 

In addition to battlefield trauma, there is also the risk of exposure to chemical weapons such as the nerve agents, notably the organophosphorus gases (soman, sarin, VX, tabun) [6]. Organophosphorus toxicity arises largely from their ability to irreversibly inhibit acetyl-cholinesterases, leading to effects associated with peripheral acetyl-choline accumulation (muscarinic syndrome) such as meiosis, profuse sweating, bradychardia, bronchioconstriction, hypotension, and diarrhoea. Central nervous system effects include anxiety, restlessness, confusion, ataxia, tremors. 

Most of the signs and symptoms resulting from diazinon poisoning are due to the inhibition of an enzyme called acetylcholinesterase in the nervous system. This enzyme is also found in your red blood cells and a similar enzyme (serum cholinesterase) is found in blood plasma. The most common test for exposure to many organophosphorus insecticides, including diazinon, is to determine the level of cholinesterase activity in the red blood cells or plasma. This test requires only a small amount of blood and is routinely available in your doctor s office. It takes time for this enzyme to completely recover to normal levels following exposure. Therefore, a valid test may be conducted a number of days following the suspected exposure. This test indicates only exposure to an insecticide of this type. It does not specifically show exposure to diazinon. 

Acetylcholine is a neurotransmitter that functions in conveying nerve impulses across synaptic clefts within the central and autonomic nervous systems and at junctures of nerves and muscles. Following transmission of an impulse across the synapse by the release of acetylcholine, acetylcholinesterase is released into the synaptic cleft. This enzyme hydrolyzes acetylcholine to choline and acetate and transmission of the nerve impulse is terminated. The inhibition of acetylcholineasterase results in prolonged, uncoordinated nerve or muscle stimulation. Organophosphorus and carbamate pesticides (Chapter 5) along with some nerve gases (i.e., sarin) elicit toxicity via this mechanism. 

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. 

Theory. Cholinesterase inhibition by organophosphorus insecticides has been the subject of several excellent reviews by O Brien (I, 2) and Heath (3). The basis of toxic action of organophosphates and carbamates in mammals is generally associated with their ability to inhibit cholinesterase in the central and peripheral nervous systems where it plays an important role in the transmission of nerve impulses. 

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). 

Pesticides are another class of chemicals capable of damaging the nervous system and, even at low levels, produce deficits detectable by psychological testing. The organophosphorus insecticides, which are chemical relatives of the most potent nerve gases, are notorious poisons and, carelessly handled, as often happens in underdeveloped countries, can prove lethal. Parathion, diazinon, and malathion are representatives of this class and are widely used in the United States. Acute poisoning episodes produce signs such as eye irritation, headache, dizziness, nausea, and visual... 

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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