1987
DOI: 10.1016/0041-008x(87)90048-2
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Comparison of serum concentrations of the acetylcholinesterase oxime reactivators HI-6, obidoxime, and PAM to efficacy against sarin (isopropyl methylphosphonofluoridate) poisoning in rats

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Cited by 40 publications
(15 citation statements)
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“…The plasma concentrations of obidoxime effective in reducing the mortality by 10-100% after administration of 3 LD5l) of sarin were estimated to be 10-55 \xM [31], a value very close to our in vitro experiments using DFP, indicating that the antidotal action of the effective dose of obidoxime depends mostly on enzyme reactivation but not on a curare like action. However, in view of the antidotal capacity of curare-like action against neostigmine-induced tetanic fade, a further increase of the dose of oxime or an addition of curare-like compounds in the therapeutic regimen for peripherally acting anti-ChE agents seems worth trying.…”
Section: Discussionsupporting
confidence: 55%
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“…The plasma concentrations of obidoxime effective in reducing the mortality by 10-100% after administration of 3 LD5l) of sarin were estimated to be 10-55 \xM [31], a value very close to our in vitro experiments using DFP, indicating that the antidotal action of the effective dose of obidoxime depends mostly on enzyme reactivation but not on a curare like action. However, in view of the antidotal capacity of curare-like action against neostigmine-induced tetanic fade, a further increase of the dose of oxime or an addition of curare-like compounds in the therapeutic regimen for peripherally acting anti-ChE agents seems worth trying.…”
Section: Discussionsupporting
confidence: 55%
“…la, table 1). This effect may be attributed to the weak anti-ChE activity of obidoxime, since obidoxime has been reported to be capable of inhibiting ChE with an IC50 of 600-3,000 pM [10,18,31], The amplitude of EPPs was not decreased by obidoxime at 100 pM but was depressed by 28% at 500 pM of obidoxime. Obidoxime depressed the amplitude of MEPPs somewhat more markedly, showing 20% inhibition at 300 pM and 50% inhibition at 500 pM (table 1 ).…”
Section: Resultsmentioning
confidence: 90%
“…29 This concentration has been assumed since then to be the minimum concentration of any oxime (regardless of identity or Shiloff and Clement reported that a serum concentration of HI-6 of only 0.72 pg ml-l (produced by an osmotic minipump) was required to protect 50% of rats against a subsequent dose of three times the L D~O of sarin (when followed immediately by atropine) . 31 The corresponding ED^^ values for toxogonin and PAM chloride were 9.05 and 2.56 pg ml-l, re~pectively.~~ Furthermore, plasma levels of HI-6 in organophosphate-poisoned patients were found to be higher for the same dose of HI-6 in unpoisoned volunteer^.^ In summary, administration of PAM or €31-6 from military autoinjectors is likely to cause little or no side-effects and produce a therapeutic concentration of oxime that persists for at least 1 h. Administration of toxogonin from an autoinjector may well cause unwanted side-effects, and the oxime may not be as effective therapeutically as other oximes at the concentration that results in vivo.…”
Section: Pharmacokineticsmentioning
confidence: 97%
“…Within the same experimental conditions, however, P2S was much less effective against ethyl N-dimethylphosphoramidocyanidate (tabun). Measuring survival in sarin poisoned rats, Shiloffand Clement (1987) found the following effective plasma concentrations (EDso values): 0.72 mg.l-1 for HI-6, 2.56 mg.l-1 for pralidoxime chloride and 9.05 mg.1-1 for obidoxime chloride. This means that for P2S the concentration of 4 mg.1-1 is not effective against all cholinesterase inhibitors and that other oximes are not necessarily effective at that concentration.…”
Section: Discussionmentioning
confidence: 99%