Acetylcholinesterase inhibitors: pharmacology and toxicology.
Article Details
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Colovic MB, Krstic DZ, Lazarevic-Pasti TD, Bondzic AM, Vasic VM
Acetylcholinesterase inhibitors: pharmacology and toxicology.
Curr Neuropharmacol. 2013 May;11(3):315-35. doi: 10.2174/1570159X11311030006.
- PubMed ID
- 24179466 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Butyric Acid Cholinesterase Protein Humans UnknownLigandDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAcetylcholinePegvisomant The risk or severity of adverse effects can be increased when Pegvisomant is combined with Acetylcholine. AcetylcholineMefloquine The risk or severity of adverse effects can be increased when Mefloquine is combined with Acetylcholine. AcetylcholineTacrine The risk or severity of adverse effects can be increased when Tacrine is combined with Acetylcholine. AcetylcholineSulpiride The risk or severity of adverse effects can be increased when Sulpiride is combined with Acetylcholine. AcetylcholineProfenamine The risk or severity of adverse effects can be increased when Profenamine is combined with Acetylcholine.