Zur Behandlung der schweren Parathion-(E 605�)-Vergiftung mit dem Cholinesterase-Reaktivator Obidoxim (Toxogonin�)

Barckow, D.; Neuhaus, G; Erdmann, W. D.

doi:10.1007/bf00577820

Cited by 34 publications

(2 citation statements)

References 7 publications

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“…Only 3-5% of the plasma concentration of C 14 labeled obidoxime was recovered in the brain of rodents (Falb and Erdmann, 1969). The brain concentration of HI6 is about 10% of its plasma concentration (Cassel et al, 1997).…”

Section: Qualitative/quantitative Determination Of Oximes At the Cerementioning

confidence: 98%

Pharmacokinetics and pharmacodynamics of some oximes and associated therapeutic consequences: a critical review

Voicu

Bajgar

Medvedovici

et al. 2010

J of Applied Toxicology

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Undoubtedly, the use of oximes represents real progress in counteracting intoxications with organophosphates (OP), through potentiating antidotal effects of atropine. The penetration extent of these compounds through the blood-brain barrier (BBB) to significantly reactivate phosphorylated or phosphonylated acetylcholinesterase (AChE) in the brain still remains a debatable issue. Penetration of biological barriers by oximes was investigated mainly through determination of several quantitative parameters characterizing digestive absorption and BBB penetration. A weak penetration of biological barriers could be concluded from the available experimental data. The functional parameters/therapeutic effects following the penetration of oximes through BBB, more precisely the antagonism of OP-induced seizures and hypothermia, prevention of brain damage and respiratory center protection, leading to the final end-point, the survival of intoxicated organisms, are of high interest. It seems obvious that oximes are weakly penetrating the BBB, with minimal brain AChE reactivation (<5%) in important functional areas, such as the ponto-medullar. The cerebral protection achieved through administration of oximes is only partial, without major impact on the antagonism of OP-induced seizures, hypothermia and respiratory center inhibition. The antidotal effects probably result from synergic effects of other PD properties, different from the brain AChE reactivation process. Oxime structures especially designed for enhanced BBB penetration, through potentiating the hydrophobic characteristics, more often produce neurotoxic effects. Certainly, obtaining oximes with broad action spectrum (active against all OP types) would make a sense, but certainly, such a target is not achievable only through the increase in their penetrability in the brain.

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Section: Qualitative/quantitative Determination Of Oximes At the Cerementioning

confidence: 98%

Pharmacokinetics and pharmacodynamics of some oximes and associated therapeutic consequences: a critical review

Voicu

Bajgar

Medvedovici

et al. 2010

J of Applied Toxicology

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“…It is at this stage of exposure that the patient is most likely to respond to therapy. Instances have been reported in which recovery of unconscious patients from very large exposures to the phosphorothionate parathion has been achieved, using atropine and obidoxime therapy over a prolonged period (Barckow, Neuhaus & Erdmann, 1969). The rate of conversion of parathion to its active metabolite, paraoxon, is of a low order (Kubistova, 1959), which would account for this success.…”

Section: Discussionmentioning

confidence: 99%

Quantitative studies of the effect of antagonists on the acute toxicity of organophosphates in rats

Natoff

Reiff

1970

British J Pharmacology

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Efficacy of obidoxime in human organophosphorus poisoning: Determination by neuromuscular transmission studies

Besser

Weilemann²,

Gutmann

1995

Muscle and Nerve

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Six patients with organophosphorus compound intoxications developed an intermediate syndrome (weakness and fasciculations) and obidoxime was given on eight occasions. The efficacy of the acetylcholinesterase (AChE) reactivator was monitored electrophysiologically by neuromuscular transmission studies using single and repetitive nerve stimulation (20 and 50 Hz) and the activity of the serum (butyryl) cholinesterase (ChE). Dramatic electrophysiologic improvement was seen when obidoxime was given early within 12 h in 3 patients, although evidence of AChE inhibition did not subside completely. When administration of obidoxime was delayed 26 h or more after intoxication on five occasions, electrophysiologic improvement was mild or absent. In one case, 66 h after intoxication with oxydemeton-S-methyl, the neuromuscular block worsened, indicating that aging of the AChE had been completed. The electrophysiologic improvement was always accompanied with better motor function but not necessarily with improvement of the overall clinical status. Serum ChE did not predict the oxime effect at the motor endplate. In humans, the efficacy of oximes in AChE reactivation can be determined rapidly using electrophysiologic studies.

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Zur Behandlung der schweren Parathion-(E 605�)-Vergiftung mit dem Cholinesterase-Reaktivator Obidoxim (Toxogonin�)

Cited by 34 publications

References 7 publications

Pharmacokinetics and pharmacodynamics of some oximes and associated therapeutic consequences: a critical review

Pharmacokinetics and pharmacodynamics of some oximes and associated therapeutic consequences: a critical review

Quantitative studies of the effect of antagonists on the acute toxicity of organophosphates in rats

Efficacy of obidoxime in human organophosphorus poisoning: Determination by neuromuscular transmission studies

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