Time-course changes of acetylcholinesterase activity in blood and some tissues in rats after intoxication by Russian VX.
The toxic effect of organophosphates is attributed to irreversible inhibition of acetylcholinesterase (AChE; EC 3.1.1.7), the enzyme that hydrolyses the neurotransmitter acetylcholine. Inhibition potency in vivo of one of the most toxic nerve agents--Russian VX (RVX;N,N-diethyl-2-[methyl-(2-methylpropoxy)phosphoryl]sulfanylethanamine) (1 x LD(50) dose administered intramuscularly, i.m.) was studied in rats. AChE in blood was inhibited by 50%, 3 min after i.m. RVX. Butylcholinesterase (BChE; EC 3.1.1.8) in plasma was inhibited less rapidly and only by 10-20%, 20 min after RVX. AChE and BChE activities in diaphragm were reduced only 35% and 15% at 30 min. While AChE and BChE activities were reduced only about 20% and 15%, respectively, the decline in activity was rapid, occurring within 3 min. These findings indicate that RVX most potently inhibits ChE outside the central nervous system.
Karasova
Jana Zdarova
JZ
Department of Toxicology, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
Bajgar
Jiri
J
Jun
Daniel
D
Pavlikova
Ruzena
R
Kuca
Kamil
K
D000110:Acetylcholinesterase / Q000097:blood*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003964:Diaphragm / Q000187:drug effects / Q000201:enzymology; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects*
D009946:Organothiophosphorus Compounds; D000110:Acetylcholinesterase; C451779:S-(N,N-diethylaminoethyl) isobutyl methylphosphothiolate