Enzyme aging and pharmacological actions of anticholinesterases
THE CONTEXT
The passage explains persistent organophosphate inhibition and contrasts the effects of lipid-soluble and lipid-insoluble anticholinesterases.
Persistence and aging of phosphorylated enzyme
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Reactivation of phosphorylated enzyme takes days, longer than the time required for enzyme regeneration.
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The phosphorylated enzyme can undergo aging through loss of one alkyl group, becoming totally resistant to hydrolysis.
Basis of pharmacological effects
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Anticholinesterase actions result from amplification of endogenous acetylcholine and are qualitatively similar to those of directly acting cholinoceptor stimulants.
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Different agents vary in the relative intensity of their muscarinic, ganglionic, skeletal muscle and central nervous system effects.
Effects according to lipid solubility
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Lipid-soluble agents, including physostigmine and organophosphates, produce more marked muscarinic and central effects. They stimulate ganglia, while skeletal muscle effects are less prominent.
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Lipid-insoluble agents, including neostigmine and other quaternary ammonium compounds, produce more marked skeletal muscle effects and also act directly on the muscle endplate.
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Lipid-insoluble agents stimulate ganglia but have less prominent muscarinic effects. They do not penetrate the central nervous system and have no central effects.