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HERO ID
7443125
Reference Type
Journal Article
Title
On the interactions between antimuscarinic atropine and NMDA receptor antagonists in anticholinesterase-treated mice
Author(s)
Dekundy, A; Blaszczak, P; Kaminski, R; Turski, WA
Year
2001
Is Peer Reviewed?
Yes
Journal
Archives of Toxicology
ISSN:
0340-5761
EISSN:
1432-0738
Volume
74
Issue
11
Page Numbers
702-708
Language
English
PMID
11218047
DOI
10.1007/s002040000189
Web of Science Id
WOS:000166744600007
Abstract
Both organophosphate (OP) and carbamate pesticides may produce seizures and death commonly attributed to the inhibition of acetylcholinesterase (AChE) and subsequent excess of acetylcholine (ACh). The anticonvulsant and neuroprotective properties of N-methyl-D-aspartate (NMDA) receptor antagonists in animals encouraged us to investigate their effects on the toxic and convulsant properties of OP and carbamate pesticides. Adult Swiss mice were systemically injected with the OP pesticide, chlorfenvinphos (CVP), or the carbamate pesticide, methomyl (MET). Both CVP and MET induced dose-dependent seizure activity and death in mice. Pretreatment with the muscarinic antagonist, atropine (ATR), at a dose of 1.8 mg/kg did not prevent seizures but decreased the lethal effects of CVP and MET. Pretreatment with the NMDA antagonists, dizocilpine (MK-801) at a dose of 1 mg/kg or 3-((R,S)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) at a dose of 10 mg/kg, influenced neither MET-induced seizures nor CVP- or MET-induced death. However, both MK-801 and CPP blocked CVP-induced seizures. Concurrent administration of ATR and the NMDA antagonists prevented seizures produced by CVP, but not those produced by MET. Nevertheless, both MK801 and CPP coadministered with ATR markedly enhanced its antilethal effects in CVP- and MET-intoxicated mice. The antidotes had no influence upon brain AChE activities in mice treated with saline or CVP or MET. It seems that combined treatment with ATR and NMDA receptor antagonists might be of clinical relevance.
Keywords
Atropine; Carbamate; Mice; NMDA antagonist; Organophosphate; 4 (3 phosphonopropyl) 2 piperazinecarboxylic acid; acetylcholine; acetylcholinesterase; atropine; carbamate pesticide; cholinesterase inhibitor; clofenvinfos; dizocilpine; methomyl; muscarinic receptor blocking agent; n methyl dextro aspartic acid receptor blocking agent; organophosphate pesticide; animal experiment; animal model; animal tissue; article; brain; controlled study; drug effect; enzyme inhibition; lethality; male; mouse; nonhuman; priority journal; seizure; toxicokinetics; treatment outcome; Acetylcholinesterase; Animals; Atropine; Brain; Chlorfenvinphos; Cholinesterase Inhibitors; Dizocilpine Maleate; Dose-Response Relationship, Drug; Drug Antagonism; Excitatory Amino Acid Antagonists; Lethal Dose 50; Male; Methomyl; Mice; Muscarinic Antagonists; Piperazines; Seizures; Animalia
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