Efficacy, toxicity and clinical use of oximes in anticholinesterase poisoning

Bismuth, C; Inns, R.H.; Marrs, Timothy C.

doi:10.1016/b978-0-7506-0271-6.50058-9

Cited by 63 publications

(44 citation statements)

References 128 publications

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“…126 Although being less toxic than TMB-4, this oxime shows hepatotoxic potential. 56,127 HI-6 is more potent than LüH-6 in protection of various rodent species from intoxication with soman, 117,119,128 as well as sarin, and especially, VX. 65 The only drawback of HI-6 is that this oxime cannot reactivate tabun-inhibited AChE.…”

Section: Drawbacks and Limitations Of Oxime Therapymentioning

confidence: 99%

“…82,103 However, AChE inhibited by several organophosphorus insecticides, including dimethoate, demethon, triamiphos, ethoprophos, profenofos, fenamiphos and pyridafenthion, resists any attempt at reactivation with any oxime, probably due to variations in phosphoryl moiety and distribution of electronic charge. 56,86,142 Finally, a systematic review of two randomized controlled clinical trials did not result in final proof of the efficacy of PAM-2 in the treatment of poisonings induced by organophosphorus insecticides in humans, 146 probably due to the methodological gaps in the trials included, as indicated in the original publication.…”

Section: Drawbacks and Limitations Of Oxime Therapymentioning

confidence: 99%

“…Namely, pralidoxime (PAM-2), the first pyridinium oxime, could reactivate the phosphylated enzyme about a million times faster than hydroxylamine. 56 By 1956, the scientific public was introduced to the use of the newly synthesized oxime, PAM-2, which was administered against parathion poisoning in Japan. 57 Further investigations in this area resulted in synthesis of bispyridinium oximes: trimedoxime (TMB-4), obidoxime (LüH-6), HI-6, and HLö-7 (figure 3).…”

Section: Oxime Therapymentioning

confidence: 99%

See 2 more Smart Citations

Unequal Efficacy of Pyridinium Oximes in Acute Organophosphate Poisoning

Antonijević¹,

Stojiljković²

2007

Clinical Medicine & Research

214

159

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Section: Drawbacks and Limitations Of Oxime Therapymentioning

confidence: 99%

Section: Drawbacks and Limitations Of Oxime Therapymentioning

confidence: 99%

Section: Oxime Therapymentioning

confidence: 99%

See 1 more Smart Citation

Unequal Efficacy of Pyridinium Oximes in Acute Organophosphate Poisoning

Antonijević¹,

Stojiljković²

2007

Clinical Medicine & Research

214

159

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“…However, regardless the greatest effort until now, only few oxime-based reactivators are used for treatment of human OP poisoning, namely pralidoxime, obidoxime and TMB-4. [57][58][59][60] Despite structurally oximes have a high structural diversity, they are nevertheless, characterized by four common basic structural characteristics: (i) charged or non-charged one or two ring systems (e.g., pyridinium, imidazole); (ii) ring(s) bearing one or more, symmetric or asymmetric oxime groups at positions 2, 3 or 4; (iii) aliphatic or aromatic side ligands attached to the ring(s); and (iv) different linkers between the rings ( Figure 2). Currently, research in the design of new types of oximes is crucial to have a therapeutic solution to OPs intoxication.…”

Section: Inhibition and Reactivation Of Esterases And Cholinesterasesmentioning

confidence: 99%

Neurotoxic Effects Associated with Current Uses of Organophosphorus Compounds

Mangas

Vilanova

Estévez

et al. 2016

Journal of the Brazilian Chemical Society

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Organophosphorus compounds (OPs) are a large and diverse class of chemicals that have been synthesized, since the XIX century for several purposes like chemical weapons, flame-retardants, ectoparasiticides and investigational new drugs, but mainly as agrochemicals in agriculture and indoor. Although the amount of OP pesticides being used is declining, especially in developed countries, OPs continue being one of the most important classes of insecticides and chemical warfare agents today due to its toxic effects on the enzyme acetylcholinesterase (AChE). Existing research on the toxicological effects of OPs is extensive, however, there is a lack of knowledge on the long-term effects of low levels of OPs and their exactly pathways of toxicity. Recent data prove that other molecular targets than AChE could be targeted by OPs, triggering these effects. Here these data are reviewed and it is highlighted that the current uses of OPs are producing several neurotoxic effects. It is also shown that, to protect people from possible uses and misuses of OPs, more regulations on OPs are needed. Moreover, more mechanistic studies are needed to completely understand their toxicological interactions and mechanisms of action and to identify the whole group of enzymes that interact with them.

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“…Together with atropine pyridinium oximes (pralidoxime, trimedoxime, obidoxime, HI-6, HLö-7) represent the most important component of the specific therapy used against organophosphate poisoning (Bismuth et al 1992;Karalliedde & Szinicz 2001). Since the resulting inhibited AChE is generally considered very stable and is only slowly reactivated by spontaneous hydrolysis of the phosphate ester, the essential role of the oximes is their ability to reactivate inhibited AChE (Worek et al 1997;Thiermann et al 1999).…”

mentioning

confidence: 99%

Efficacy of Trimedoxime in Mice Poisoned with Dichlorvos, Heptenophos or Monocrotophos

Antonijević

Bokonjić²,

Stojiljković³

et al. 2005

Basic Clin Pharma Tox

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The aim of the study was to examine antidotal potency of trimedoxime in mice poisoned with three direct dimethoxy-substituted organophosphorus inhibitors. In order to assess the protective efficacy of trimedoxime against dichlorvos, heptenophos or monocrotophos, median effective doses and efficacy half-times were calculated. Trimedoxime (24 mg/kg intravenously) was injected 5 min. before 1.3 LD50 intravenously of poisons. Activities of brain, diaphragmal and erythrocyte acetylcholinesterase, as well as of plasma carboxylesterases were determined at different time intervals (10, 40 and 60 min.) after administration of the antidotes. Protective effect of trimedoxime decreased according to the following order: monocrotophos Ͼ heptenophos Ͼ dichlorvos. Administration of the oxime produced a significant reactivation of central and peripheral acetylcholinesterase inhibited with dichlorvos and heptenophos, with the exception of erythrocyte acetylcholinesterase inhibited by heptenophos. Surprisingly, trimedoxime did not induce reactivation of monocrotophos-inhibited acetylcholinesterase in any of the tissues tested. These organophosphorus compounds produced a significant inhibition of plasma carboxylesterase activity, while administration of trimedoxime led to regeneration of the enzyme activity. The same dose of trimedoxime assured survival of experimental animals poisoned by all three organophosphorus compounds, although the biochemical findings were quite different.

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Efficacy, toxicity and clinical use of oximes in anticholinesterase poisoning

Cited by 63 publications

References 128 publications

Unequal Efficacy of Pyridinium Oximes in Acute Organophosphate Poisoning

Unequal Efficacy of Pyridinium Oximes in Acute Organophosphate Poisoning

Neurotoxic Effects Associated with Current Uses of Organophosphorus Compounds

Efficacy of Trimedoxime in Mice Poisoned with Dichlorvos, Heptenophos or Monocrotophos

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