Acetylcholinesterase Inhibitors: Pharmacology and Toxicology
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Autori
Čolović, Mirjana B.Krstić, Danijela Z.
Lazarević-Pašti, Tamara
Bondžić, Aleksandra M.
Vasić, Vesna M.
Članak u časopisu
Metapodaci
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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 Alzheimers disease, and toxic carbamates used as pesticides. Subsequently, mechanism of irreversible acet...ylcholinesterase 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.
Ključne reči:
acetylcholine / acetylcholinesterase / Alzheimers disease drugs / carbamates / detoxification / irreversible inhibitors / organophosphates / reversible inhibitorsIzvor:
Current Neuropharmacology, 2013, 11, 3, 315-335Finansiranje / projekti:
- Istraživanja interakcija enzima sa toksičnim i farmakološki aktivnim molekulima (RS-MESTD-Basic Research (BR or ON)-172023)
DOI: 10.2174/1570159X11311030006
ISSN: 1570-159X; 1875-6190
PubMed: 24179466
WoS: 000318152300006
Scopus: 2-s2.0-84878657720
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Institucija/grupa
VinčaTY - JOUR AU - Čolović, Mirjana B. AU - Krstić, Danijela Z. AU - Lazarević-Pašti, Tamara AU - Bondžić, Aleksandra M. AU - Vasić, Vesna M. PY - 2013 UR - https://vinar.vin.bg.ac.rs/handle/123456789/5474 AB - 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 Alzheimers 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. T2 - Current Neuropharmacology T1 - Acetylcholinesterase Inhibitors: Pharmacology and Toxicology VL - 11 IS - 3 SP - 315 EP - 335 DO - 10.2174/1570159X11311030006 ER -
@article{ author = "Čolović, Mirjana B. and Krstić, Danijela Z. and Lazarević-Pašti, Tamara and Bondžić, Aleksandra M. and Vasić, Vesna M.", year = "2013", 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 Alzheimers 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.", journal = "Current Neuropharmacology", title = "Acetylcholinesterase Inhibitors: Pharmacology and Toxicology", volume = "11", number = "3", pages = "315-335", doi = "10.2174/1570159X11311030006" }
Čolović, M. B., Krstić, D. Z., Lazarević-Pašti, T., Bondžić, A. M.,& Vasić, V. M.. (2013). Acetylcholinesterase Inhibitors: Pharmacology and Toxicology. in Current Neuropharmacology, 11(3), 315-335. https://doi.org/10.2174/1570159X11311030006
Čolović MB, Krstić DZ, Lazarević-Pašti T, Bondžić AM, Vasić VM. Acetylcholinesterase Inhibitors: Pharmacology and Toxicology. in Current Neuropharmacology. 2013;11(3):315-335. doi:10.2174/1570159X11311030006 .
Čolović, Mirjana B., Krstić, Danijela Z., Lazarević-Pašti, Tamara, Bondžić, Aleksandra M., Vasić, Vesna M., "Acetylcholinesterase Inhibitors: Pharmacology and Toxicology" in Current Neuropharmacology, 11, no. 3 (2013):315-335, https://doi.org/10.2174/1570159X11311030006 . .