Informacja

Drogi użytkowniku, aplikacja do prawidłowego działania wymaga obsługi JavaScript. Proszę włącz obsługę JavaScript w Twojej przeglądarce.

Przeglądasz jako GOŚĆ
Tytuł pozycji:

Assessment of false transmitters as treatments for nerve agent poisoning.

Tytuł :
Assessment of false transmitters as treatments for nerve agent poisoning.
Autorzy :
Whitmore C; Chemical, Biological and Radiological Division, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK. Electronic address: .
Lindsay CD; Chemical, Biological and Radiological Division, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK.
Bird M; Chemical, Biological and Radiological Division, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK.
Gore SJ; Chemical, Biological and Radiological Division, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK.
Rice H; Chemical, Biological and Radiological Division, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK.
Williams RL; Chemical, Biological and Radiological Division, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK.
Timperley CM; Chemical, Biological and Radiological Division, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK.
Green AC; Chemical, Biological and Radiological Division, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, Wiltshire, SP4 0JQ, UK.
Pokaż więcej
Źródło :
Toxicology letters [Toxicol Lett] 2020 Mar 15; Vol. 321, pp. 21-31. Date of Electronic Publication: 2019 Dec 09.
Typ publikacji :
Journal Article
Język :
English
Journal Info :
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7709027 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3169 (Electronic) Linking ISSN: 03784274 NLM ISO Abbreviation: Toxicol. Lett. Subsets: MEDLINE
Imprint Name(s) :
Publication: Amsterdam : Elsevier
Original Publication: Amsterdam, Elsevier/North Holland.
MeSH Terms :
Acetylcholine/*analogs & derivatives
Antidotes/*pharmacology
Choline/*analogs & derivatives
Cholinesterase Inhibitors/*poisoning
Diaphragm/*innervation
Nerve Agents/*poisoning
Neurotransmitter Agents/*pharmacology
Organophosphate Poisoning/*drug therapy
Soman/*poisoning
Synapses/*drug effects
Acetylcholine/chemical synthesis ; Acetylcholine/metabolism ; Acetylcholine/pharmacology ; Acetylcholinesterase/metabolism ; Animals ; Antidotes/chemical synthesis ; CHO Cells ; Cell Line, Tumor ; Choline/chemical synthesis ; Choline/pharmacology ; Cricetulus ; Drug Partial Agonism ; Guinea Pigs ; Humans ; Male ; Neurotransmitter Agents/chemical synthesis ; Organophosphate Poisoning/enzymology ; Organophosphate Poisoning/physiopathology ; Receptors, Cholinergic/drug effects ; Receptors, Cholinergic/genetics ; Receptors, Cholinergic/metabolism ; Synapses/enzymology
Contributed Indexing :
Keywords: Acetylcholine; False transmitters; Nerve agent; Nerve agent treatments; Nicotinic acetylcholine receptors; Soman
Substance Nomenclature :
0 (Antidotes)
0 (Cholinesterase Inhibitors)
0 (Nerve Agents)
0 (Neurotransmitter Agents)
0 (Receptors, Cholinergic)
40792-85-6 (acetylmonoethylcholine)
54378-00-6 (acetyldiethylcholine)
96-64-0 (Soman)
EC 3.1.1.7 (Acetylcholinesterase)
N91BDP6H0X (Choline)
N9YNS0M02X (Acetylcholine)
Entry Date(s) :
Date Created: 20191213 Date Completed: 20200127 Latest Revision: 20200127
Update Code :
20200716
DOI :
10.1016/j.toxlet.2019.12.010
PMID :
31830555
Czasopismo naukowe
Nerve agents inhibit acetylcholinesterase (AChE), leading to a build-up of acetylcholine (ACh) and overstimulation at cholinergic synapses. Current post-exposure nerve agent treatment includes atropine to treat overstimulation at muscarinic synapses, a benzodiazepine anti-convulsant, and an oxime to restore the function of AChE. Aside from the oxime, the components do not act directly to reduce the overstimulation at nicotinic synapses. The false transmitters acetylmonoethylcholine (AMECh) and acetyldiethylcholine (ADECh) are analogs of ACh, synthesised similarly at synapses. AMECh and ADECh are partial agonists, with reduced activity compared to ACh, so it was hypothesised the false transmitters could reduce overstimulation. Synthetic routes to AMECh and ADECh, and their precursors, monoethylcholine (MECh) and diethylcholine (DECh), were devised, allowing them to be produced easily on a laboratory-scale. The mechanism of action of the false transmitters was investigated in vitro. AMECh acted as a partial agonist at human muscarinic (M 1 and M 3 ) and muscle-type nicotinic receptors, and ADECh was a partial agonist only at certain muscarinic subtypes. Their precursors acted as antagonists at muscle-type nicotinic, but not muscarinic receptors. Administration of MECh and DECh improved neuromuscular function in the soman-exposed guinea-pig hemi-diaphragm preparation. False transmitters may therefore help reduce nerve agent induced overstimulation at cholinergic synapses.
(Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Ta witryna wykorzystuje pliki cookies do przechowywania informacji na Twoim komputerze. Pliki cookies stosujemy w celu świadczenia usług na najwyższym poziomie, w tym w sposób dostosowany do indywidualnych potrzeb. Korzystanie z witryny bez zmiany ustawień dotyczących cookies oznacza, że będą one zamieszczane w Twoim komputerze. W każdym momencie możesz dokonać zmiany ustawień dotyczących cookies