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.

• MeSH
• acetylcholinesterasa krev   MeSH
• bránice účinky léků   enzymologie   MeSH
• časové faktory MeSH
• chování zvířat účinky léků   MeSH
• játra účinky léků   enzymologie   MeSH
• krysa rodu Rattus MeSH
• LD50 MeSH
• mozek účinky léků   enzymologie   MeSH
• organothiofosforové sloučeniny toxicita   MeSH
• potkani Wistar MeSH
• tkáňová distribuce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• organothiofosforové sloučeniny MeSH
• S-(N,N-diethylaminoethyl) isobutyl methylphosphothiolate MeSH Prohlížeč

Seven new oxime-based acetylcholinesterase reactivators were compared with three currently available ones (obidoxime, trimedoxime, HI-6) for their ability to lessen cholinesterase inhibition in blood and brain of cyclosarin-treated rats. Oximes were given at doses of 5% their LD(50) along with 21 mg/kg atropine five min before the LD(50) of cyclosarin (120 ug/kg) was administered. Blood and brain samples were collected 30 minutes later. The greatest difference between acetylcholinesterase inhibition in blood of cyclosarin-treated rats was found after administration of HI-6 (40%), compared to 22% for trimedoxime and 6% for obidoxime. Only two of the seven newly synthesized oximes had any effect (K203 at 7%, K156 at 5%). Effective oximes against cyclosarin-inhibited plasma butyrylcholinesterase were HI-6 (42%), trimedoxime (11%), and K156 (4%). The oximes were less effective in brain than in blood, with reactivation values for HI-6 30% against acetylcholinesterase and 10% against butyrylcholinesterase. Values for newly synthesized oximes were less than 10% for K206, K269 and K203.

• Klíčová slova
• acetylcholinesterase, butyrylcholinesterase, cyclosarin, oximes, reactivators,
• MeSH
• acetylcholinesterasa krev   metabolismus   MeSH
• atropin farmakologie   MeSH
• krysa rodu Rattus MeSH
• mozek účinky léků   enzymologie   MeSH
• organofosforové sloučeniny toxicita   MeSH
• oximy chemie   farmakologie   MeSH
• potkani Wistar MeSH
• reaktivátory cholinesterasy chemie   farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• atropin MeSH
• cyclohexyl methylphosphonofluoridate MeSH Prohlížeč
• organofosforové sloučeniny MeSH
• oximy MeSH
• reaktivátory cholinesterasy MeSH

The therapeutical efficacies of eleven oxime-based acetylcholinesterase reactivators were compared in an in vivo (rat model) study of treatment of intoxication caused by tabun. In this group there were some currently available oximes (obidoxime, trimedoxime and HI-6) and the rest were newly synthesized compounds. The best reactivation efficacy for acetylcholinesterase in blood (expressed as percent of reactivation) among the currently available oximes was observed after administration of trimedoxime (16%) and of the newly synthesized K127 (22432) (25%). The reactivation of butyrylcholinesterase in plasma was also studied; the best reactivators were trimedoxime, K117 (22435), and K127 (22432), with overall reactivation efficacies of approximately 30%. Partial protection of brain ChE against tabun inhibition was observed after administration of trimedoxime (acetylcholinesterase 20%; butyrylcholinesterase 30%) and obidoxime (acetylcholinesterase 12%; butyrylcholinesterase 16%).

• Klíčová slova
• Acetylcholinesterase, butyrylcholinesterase, oximes, pretreatment, reactivators,
• Publikační typ
• časopisecké články MeSH