Cholinesterase and carboxylesterase activities in soman poisoned rats treated with bispyridinium mono-oximes HI-6 and HS-6

Sterri, Sigrun H.; Lyngaas, Synnøve; Fonnum, Frode

doi:10.1016/0006-2952(83)90342-8

Cited by 19 publications

(4 citation statements)

References 19 publications

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“…HI-6 seems to act primarily in the periphery by reactivation of phosphylated cholinesterase before dealkylation (aging) has occurred (Sterri et al 1983;Shih et al 1991), although some recently published results have directed the attention to other possible direct effects of this oxime (Hamilton and Lundy 1989;Van Helden et al 1991).…”

Section: Introductionmentioning

confidence: 96%

Effect of pyridostigmine pretreatment, HI-6 and toxogonin (®) treatment on rat tracheal smooth muscle response to cholinergic stimulation after organophosphorus inhalation exposure

Walday

Aas

Haider³

et al. 1993

Arch Toxicol

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The ex vivo contraction response of the rat tracheal smooth muscle was examined after 10 min in vivo inhalation of soman and/or pretreatment with pyridostigmine and/or post-exposure treatment with HI-6 ([[[(4-aminocarbonyl)pyridinio]methoxy]methyl]-2[(hydroxy imino) methyl]pyridinium dichloride) or Toxogonin (1,1'-[oxybis-(methylene)]bis[4-[(hydroxyimino)methyl]-py rid inium] dichloride). In vivo pretreatment with pyridostigmine was achieved by subcutaneous (s.c.) implantation of an osmotic pump that delivered pyridostigmine continuously (0.01 mg/h) in the neck region of the rat 18 h before soman exposure. The ex vivo cholinergic tracheal smooth muscle response increased during the first 60 min after soman exposure in animals pretreated with pyridostigmine. The amplitude of the contraction response in pyridostigmine pretreated animals was about 60% of control, compared to 15% of control without pyridostigmine pretreatment. Pyridostigmine pretreatment also produced significant recovery of the total cholinesterase (ChE) activity in plasma, but not in trachea and lung. Intraperitoneal (i.p.) injection of HI-6 or Toxogonin (50 mg/kg), immediately after 10 min inhalation exposure to soman, also significantly improved the ex vivo cholinergic contraction response of the trachea (decapitation 15 min after oxime administration). The recovery of the physiological response with Toxogonin was, however, not stable. HI-6 was superior to Toxogonin with respect to the initial airway contraction response, and the response increased up to a stable level not significantly different from control. There was no significant reactivation of the ChE activity after treatment with the oximes. Combination of pyridostigmine pretreatment and oxime treatment enhanced the recovery of the tracheal contraction response and the ChE activity in the trachea compared to treatment with oximes alone.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Introductionmentioning

confidence: 96%

Effect of pyridostigmine pretreatment, HI-6 and toxogonin (®) treatment on rat tracheal smooth muscle response to cholinergic stimulation after organophosphorus inhalation exposure

Walday

Aas

Haider³

et al. 1993

Arch Toxicol

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“…Oximeinduced reactivation of OP-inhibited AChE and BuChE have been extensively studied and recently reviewed (9,10). However, reactivation of OP-inhibited CaE has been studied in only a few papers (4,11,12). These studies have established that in vivo oxime-induced reactivation of OP-inhibited plasma carboxylesterase provides protection against soman and sarin in rats.…”

Section: Introductionmentioning

confidence: 99%

Oxime-Induced Reactivation of Carboxylesterase Inhibited by Organophosphorus Compounds

Maxwell¹,

Lieske²,

Brecht³

1994

Chem. Res. Toxicol.

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A structure-activity analysis of the ability of oximes to reactivate rat plasma carboxylesterase (CaE) that was inhibited by organophosphorus (OP) compounds revealed that uncharged oximes, such as diacetylmonoxime or monoisonitrosoacetone, were better reactivators than cationic oximes.Cationic oximes that are excellent reactivators of OP-inhibited acetylcholinesterase, such as pyridinium-2-aldoxime or the bispyridinium oximes, HI-6 and TMB-4, produced poor reactivation of OP-inhibited CaE.The best uncharged reactivator was diacetylmonoxime which produced complete reactivation at 0.3 mM in 2 hr of CaE that was inhibited by organophosphinates, alkoxycontaining phosphates, and alkoxy-containing phosphonates. Complete reactivation of CaE could be achieved even after inhibition by phosphonates with highly branched alkoxy groups, such as sarin and soman, that undergo rapid aging with acetylcholinesterase.CaE that was inhibited by phosphonates or phosphates that contained aryloxy groups were reactivated to a lower extent.The cause of this decreased reactivation appears to be an oxime-induced aging reaction that competes with the reactivation reaction.This oxime-induced aging reaction is accelerated by electron-withdrawing substituents on the aryloxy groups of phosphonates and by the presence of multiple aryloxy groups on phosphates.Thus, reactivation and aging of OP-inhibited CaE differ from the same processes for OP-inhibited acetyicholinesterase in both their oxime specificity and inhibitor specificity and, presumably, in their underlying mechanisms. 94-08715 IIIIIIIIIIUE = a82CCGPONENT PART NOTICE

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“…The standard oximes available today as antidotes are obidoxime (toxogonin), HI-6 and TMB-4. The oxime HI-6 has been reported as an effective reactivator of non-aged soman inhibited human AChE [18][19][20][21] . Further an effective therapy by a single oxime for a broad spectrum of OP pesticides and nerve agents is still lacking.…”

Section: Introduction Organophosphorus (Op) Pesticides Such As Oodiementioning

confidence: 99%

“…Oximes such as 2-(Hydroxyiminomethyl)-1-methylpyridinium chloride (2-PAM) and several other oximes are developed in the past as reactivators for OP poisoning 13,14 11,[16][17] . Mono-and bis-pyridinium oximes have been used as AChE reactivators in OP intoxication 18,19 . The standard oximes available today as antidotes are obidoxime (toxogonin), HI-6 and TMB-4.…”

Section: Introduction Organophosphorus (Op) Pesticides Such As Oodiementioning

confidence: 99%

In-vitro Evaluation of Bis-pyridinium Oximes Connected by Xylene Linkers as Reactivators of DFP-inhibited Electric EEL Acetylcholinesterase

et al. 2016

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Bis-pyridinium oximes connected by xylene linkers were synthesised and their in-vitro reactivation efficacy was evaluated for DFP inhibited AChE. The reactivation efficacy data were compared with those of 2-PAM and obidoxime. However, it was observed that none of these oximes were able to surpass the reactivation efficacy of 2-PAM and obidoxime in reactivating DFP inhibited AChE. 2-PAM and obidoxime respectively exhibited 52 per cent and 43 per cent reactivation of DFP inhibited AChE, where as the synthesised oximes 3a, 3d, and 3f showed 37 per cent, 30 per cent, and 31 per cent reactivation, respectively within 10 min at 10 -3 M.Keywords: Bis-pyridinium oximes, Reactivators, 2-PAM, DFP, organophosphorus pesticides, nerve agents, acetylcholinesterase, obidoxime Figure 1. organophosphorus pesticides and nerve agents.

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Cholinesterase and carboxylesterase activities in soman poisoned rats treated with bispyridinium mono-oximes HI-6 and HS-6

Cited by 19 publications

References 19 publications

Effect of pyridostigmine pretreatment, HI-6 and toxogonin (®) treatment on rat tracheal smooth muscle response to cholinergic stimulation after organophosphorus inhalation exposure

Effect of pyridostigmine pretreatment, HI-6 and toxogonin (®) treatment on rat tracheal smooth muscle response to cholinergic stimulation after organophosphorus inhalation exposure

Oxime-Induced Reactivation of Carboxylesterase Inhibited by Organophosphorus Compounds

In-vitro Evaluation of Bis-pyridinium Oximes Connected by Xylene Linkers as Reactivators of DFP-inhibited Electric EEL Acetylcholinesterase

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