Therapeutic efficacy of HI-6 in soman-poisoned marmoset monkeys

Helden, H.P.M. van; Wiel, H.J. van der; Lange, Jan de; Busker, Ruud W.; Melchers, B.P.C.; Wolthuis, Otto L.

doi:10.1016/0041-008x(92)90366-z

Cited by 50 publications

(21 citation statements)

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“…The data confirmed earlier reported findings in vivo and in vitro that this oxime reactivates unaged soman-inhibited AChE in other animal species (De Jong and Wolring 1980;Clement 1981;Harris et al 1990;van Helden et al 1992). In addition, other studies have consistently demonstrated that HI-6 is effective as an oxime therapy in the presence of atropine in protecting against multiple LD50s of soman across a number of animal species, including non-human primates (Clement 1981;Inns andLeadbeater 1983, Boskovic et al 1984;Shih et al 1986Shih et al , 1991Hamilton and Lundy 1989;Harris et al 1990;van Helden et al 1992). Therefore, it is likely that the increased activity of AChE in the periphery contributes to the survival of soman-intoxicated animals.…”

Section: Discussionsupporting

confidence: 93%

“…The antidotal effect of H-oxime is reported to be due in large part to its ability to reactivate or protect ChE from inhibition by soman in blood and peripheral tissues/organs of several animal species (Clement 1981;Shih et al 1986Shih et al , 1991Harris et al 1990;van Helden et al 1992). Similarly, the beneficial effect of pyridostigmine is due to its reversible inhibition of peripheral ChE, thus protecting a portion of the enzyme from irreversible phosphorylation by soman (Berry and Davies 1970;Gordon et al 1978).…”

Section: Discussionmentioning

confidence: 87%

“…When used in combination with atropine sulfate, HI-6 has been shown to protect against multiple LDs0s of soman in a number of species including mice, rats, guinea pigs, dogs and non-human primates (Clement 1981;Inns and Leadbeater 1983;Boskovic et al 1984;Shih et al 1986Shih et al , 1991Hamilton and Lundy 1989;van Helden et al 1992). Most recently HI-6 has been used with some success in Yugoslavia to replace 2-PAM in human intoxication by commercial preparations of OP insecticides (Jovanovic et al 1990; Kusic et al 1991).…”

Section: Introductionmentioning

confidence: 93%

“…Most recently HI-6 has been used with some success in Yugoslavia to replace 2-PAM in human intoxication by commercial preparations of OP insecticides (Jovanovic et al 1990; Kusic et al 1991). Current neurochemical findings strongly suggest that reactivation by HI-6 of soman-inhibited ChE contributes to the survival of intoxicated animals (Shih et al 1991;van Helden et al 1992).…”

Section: Introductionmentioning

confidence: 96%

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Comparison of several oximes on reactivation of soman-inhibited blood, brain and tissue cholinesterase activity in rats

Shih¹

1993

Arch Toxicol

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The ability of three oximes, HI-6, MMB-4 and ICD-467, to reactivate cholinesterase (ChE) inhibited by the organophosphorus compound soman was compared in blood (plasma and erythrocytes), brain regions (including spinal cord) and peripheral tissues of rats. Animals were intoxicated with soman (100 micrograms/kg, SC; equivalent to 0.9 x LD50 dose) and treated 1 min later with one of these oximes (100 or 200 mumol/kg, IM). Toxic sign scores and total tissue ChE activities were determined 30 min later. Soman markedly inhibited ChE activity in blood (93-96%), brain regions (ranging from 78% to 95%), and all peripheral tissues (ranging from 48.9% to 99.8%) except liver (11.9%). In blood, treatment with HI-6 or ICD-467 resulted in significant reactivation of soman-inhibited ChE. In contrast, MMB-4 was completely ineffective. HI-6 and ICD-467 were equally effective at the high dose. At the low dose ICD-467 treatment resulted in significantly higher plasma ChE than HI-6 treatment, whereas HI-6 treatment resulted in higher erythrocyte ChE than ICD-467 treatment. However, none of these three oximes reactivated or protected soman-inhibited ChE in the brain. In all peripheral tissues (except liver) studied, MMB-4 was not effective. HI-6 reactivated soman-inhibited ChE in all tissues except lung, heart, and skeletal muscle. ICD-467 was highly effective in reactivating ChE in all tissues and afforded a complete recovery of ChE to control levels in intercostal muscle and salivary gland. Oxime treatments did not modify the toxic scores produced by soman. However, treatment with the high dose (200 mumol/kg) of ICD-467 depressed respiration and two of the six rats died in 10 min. These observations indicate that MMB-4 is completely ineffective in protecting and/or reactivating soman-inhibited ChE, HI-6 is an effective ChE reactivator as reported earlier in rats and other species, and the imidazolium oxime ICD-467 is a powerful reactivator of soman-inhibited ChE; however, its toxic interactions with soman may not be related to tissue ChE levels.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 96%

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Comparison of several oximes on reactivation of soman-inhibited blood, brain and tissue cholinesterase activity in rats

Shih¹

1993

Arch Toxicol

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“…soman) still exist (30)(31)(32)(33)(34)(35)(36). Aside from an unknown direct oxime reaction, recovery of muscle force was mainly attributed to the reactivation of inhibited muscle AChE.…”

Section: Investigation Of Neuromuscular Transmissionmentioning

confidence: 99%

Red Blood Cell Acetylcholinesterase and Plasma Butyrylcholinesterase Status: Important Indicators for the Treatment of Patients Poisoned by Organophosphorus Compounds

Thiermann

Kehe

Steinritz

et al. 2007

Archives of Industrial Hygiene and Toxicology

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Red Blood Cell Acetylcholinesterase and Plasma Butyrylcholinesterase Status: Important Indicators for the Treatment of Patients Poisoned by Organophosphorus CompoundsInhibition of acetylcholinesterase (AChE) is regarded as the primary toxic mechanism of organophosphorus compounds (OP). Therapeutic strategies are directed to antagonise overstimulation of muscarinic receptors with atropine and to reactivate inhibited AChE with oximes. Reactivation is crucial within the neuromuscular synapse, where atropine is ineffective, since peripheral neuromuscular block eventually leads to respiratory failure. Patients with OP intoxication have to be identified as early as possible.During an international NBC-defence exercise anesthetised pigs were poisoned with sarin, followed by treatment with atropine and oxime. Blood samples were drawn and red blood cell (RBC)-AChE activity determined with a fielded test system on-site. Within a few minutes the poisoning was verified. After administration of HI-6, RBC-AChE activity increased rapidly. Blood samples were reanalysed in our laboratory in Munich. Almost identical course of the AChE activities was recorded by both systems.The more comprehensive cholinesterase status was determined in Munich. Oxime administration can be stopped when AChE is aged completely, but has to be continued as long as poison is present in the body and reactivation is possible.To aid the on-site physician in optimising diagnosis and treatment, a fielded test system should be available to allow rapid determination of the complete cholinesterase status.

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Medical Treatment of Poisoning with Organophosphates and Carbamates

Jokanović¹

2011

Anticholinesterase Pesticides

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Therapeutic efficacy of HI-6 in soman-poisoned marmoset monkeys

Cited by 50 publications

References 20 publications

Comparison of several oximes on reactivation of soman-inhibited blood, brain and tissue cholinesterase activity in rats

Comparison of several oximes on reactivation of soman-inhibited blood, brain and tissue cholinesterase activity in rats

Red Blood Cell Acetylcholinesterase and Plasma Butyrylcholinesterase Status: Important Indicators for the Treatment of Patients Poisoned by Organophosphorus Compounds

Medical Treatment of Poisoning with Organophosphates and Carbamates

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