Antagonists acetylcholinesterase

It is well established that acetylcholine can be catabolized by both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) these are also known as "true" and "pseudo" cholinesterase, respectively. Such enzymes may be differentiated by their specificity for different choline esters and by their susceptibility to different antagonists. They also differ in their anatomical distribution, with AChE being associated with nervous tissue while BChE is largely found in non-nervous tissue. In the brain there does not seem to be a good correlation between the distribution of cholinergic terminals and the presence of AChE, choline acetyltransferase having been found to be a better marker of such terminals. An assessment of cholinesterase activity can be made by examining red blood cells, which contain only AChE, and plasma. 

Gilani, A. H., Ghayur, M. N., Khalid, A., Haq, Z., Choudhary, M. I. and Rahman, A. 2005. Presence of antispasmodid, antidiarrheal, antisecretory. Calcium antagonist and acetylcholinesterase inhibitory steroidal alkaloids in Sarcococca saligna. Planta Medica, 71 120-125. 

Synaptic Clearance Antagonists. By preventing the removal of naturally-released transmitter from the region of its receptors, the effect of the neuromesssenger on the receiving cell will be prolonged and intensified. There are three principal routes by which neuromessengers are removed from the synaptic cleft (i) enzymatic destruction of the transmitter (e.g., acetylcholine (ACh) which is hydrolyzed in the synaptic cleft by acetylcholinesterase) (ii) uptake into pre- and post- synaptic cells by membrane-associated pumps that have substantial specificty for molecules they will carry (iii) diffusion away from the cleft. 

The authors speculated that the antimuscarinic drugs impaired the cholinergic receptor down-regulation that would normally occur in the presence of the increased concentrations of acetylcholine caused by acetylcholinesterase inhibition. Withdrawal of the antagonist therefore abruptly exposed the receptors to high concentrations of the neurotransmitter, leading to seizures. 

The recommended treatment in cases of acute poisoning is symptomatic. It is important to monitor and support breathing if signs of respiratory paralysis appear and to monitor blood pressure and pulse rate, since bradycardia and hypotonia may occur. Since imidacloprid does not inhibit acetylcholinesterase activity, treatment with a reactivating oxime (e.g., pralidoxime) is not indicated. Furthermore, treatment with a nicotinic antagonist may be ineffective or potentially harmful since symptoms of poisoning may be mediated by stimulation or inhibition of various nicotinic receptor subtypes or by other possible mechanisms. 

Pyriminil toxicity occurs primarily because it inhibits NADH ubiquinone oxidoreductase activity of complex I in mammalian mitochondria resulting in preferential toxicity to high-energy-demanding cells such as nerves and pancreatic jS-cells. However, pyriminil may also act as a nicotinamide antagonist and interfere with the synthesis of NADH/NADPH, furthering neural and jS-cell toxicity. Inhibition of mitochondrial respiration in nerves causes somatic, autonomic, and central nervous system neuropathies while inhibition in jS-cell causes an immediate, irreversible insulin-dependent diabetes mellitus condition. Pyriminil also acts as a noncompetitive inhibitor of rat acetylcholinesterase. 

Anticholinesterases are antagonists of the enzyme acetylcholinesterase—the enzyme which hydrolyses acetylcholine. If acetylcholine is not destroyed, it can return to activate the cholinergic receptor again and so the effect of an anticholinesterase is to increase levels of acetylcholine and to increase cholinergic effects (Fig. 11.44). 

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