Cholinesterase reactivators: the fate and effects in the organism poisoned with organophosphates/nerve agents
Language English Country Netherlands Media print
Document type Journal Article
- MeSH
- Acetylcholine analysis MeSH
- Antidotes administration & dosage chemistry therapeutic use MeSH
- Cholinesterases drug effects MeSH
- Diazepam therapeutic use MeSH
- Blood-Brain Barrier drug effects MeSH
- Humans MeSH
- Molecular Structure MeSH
- Neurotransmitter Agents pharmacokinetics poisoning MeSH
- Organophosphorus Compounds pharmacokinetics MeSH
- Organophosphate Poisoning MeSH
- Oximes administration & dosage chemistry pharmacokinetics MeSH
- Pesticides chemistry pharmacokinetics MeSH
- Cholinesterase Reactivators administration & dosage chemistry pharmacokinetics therapeutic use MeSH
- Seizures drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Acetylcholine MeSH
- Antidotes MeSH
- Cholinesterases MeSH
- Diazepam MeSH
- Neurotransmitter Agents MeSH
- Organophosphorus Compounds MeSH
- Oximes MeSH
- Pesticides MeSH
- Cholinesterase Reactivators MeSH
Understanding the mechanism of action of organophosphates (OP)/nerve agents -- irreversible acetylcholinesterase (AChE, EC 3.1.1.7) inhibition at the cholinergic synapses followed by metabolic dysbalance of the organism -- two therapeutic principles for antidotal treatment are derived. The main drugs are anticholinergics that antagonize the effects of accumulated acetylcholine at the cholinergic synapses and cholinesterase reactivators (oximes) reactivating inhibited AChE. Anticonvulsants such as diazepam are also used to treat convulsions. Though there are experimental data on a good therapeutic effects of reactivators, some attempts to underestimate the role of reactivators as effective antidotes against OP poisoning have been made. Some arguments on the necessity of their administration following OP poisoning are discussed. Their distribution patterns and some metabolic and pharmacological effects are described with the aim to resolve the question on their effective use, possible repeated administration in the treatment of OP poisoning, their peripheral and central effects including questions on their penetration through the blood brain barrier as well as a possibility to achieve their effective concentration for AChE reactivation in the brain. Reactivation of cholinesterases in the peripheral and central nervous system is described and it is underlined its importance for the survival or death of the organism poisoned with OP. Metabolization and some other effects of oximes (not connected with AChE reactivation) are discussed (e.g. forming of the phosphonylated oxime, parasympatholytic action, hepatotoxicity, behavioral changes etc.). An universality of oximes able to reactivate AChE inhibited by all OP is questioned and therefore, needs of development of new oximes is underlined.
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