Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the
neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The
enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and
muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the
enzyme as their primary target, are applied as relevant drugs and toxins. This review presents an overview of toxicology
and pharmacology of reversible and irreversible acetylcholinesterase inactivating compounds. In the case of reversible
inhibitors being commonly applied in neurodegenerative disorders treatment, special attention is paid to currently
approved drugs (donepezil, rivastigmine and galantamine) in the pharmacotherapy of Alzheimer’s disease, and toxic
carbamates used as pesticides. Subsequently, mechanism of irreversible acetylcholinesterase inhibition induced by
organophosphorus compounds (insecticides and nerve agents), and their specific and nonspecific toxic effects are
described, as well as irreversible inhibitors having pharmacological implementation. In addition, the pharmacological
treatment of intoxication caused by organophosphates is presented, with emphasis on oxime reactivators of the inhibited
enzyme activity administering as causal drugs after the poisoning. Besides, organophosphorus and carbamate insecticides
can be detoxified in mammals through enzymatic hydrolysis before they reach targets in the nervous system.
Carboxylesterases most effectively decompose carbamates, whereas the most successful route of organophosphates
detoxification is their degradation by corresponding phosphotriesterases.