In vitro effects of toxogonin, HI-6 and HLö-7 on the release of [3H]acetylcholine from peripheral cholinergic nerves in rat airway smooth muscle

Aas, Pål

doi:10.1016/0014-2999(96)00027-1

Cited by 13 publications

(3 citation statements)

References 39 publications

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“…Interaction with ACh receptors is another way of how HI-6 can be implicated in neuromodulation (Soukup et al, 2008). The antagonist effect of another oxime reactivator, obidoxime, to muscarinic ACh receptor has been also been shown (Aas, 1996). It can be hypothesized that HI-6 regulates parasympathaticus in the blood system as its termination, the cholinergic anti-inflammatory pathway, includes both molecules: the nicotinic ACh receptor and AChE (Rosas-Ballina et al, 2009).…”

Section: Discussionmentioning

confidence: 97%

Investigation of oxidative stress in blood, brain, kidney, and liver after oxime antidote HI-6 application in a mouse experimental model

Pohanka

Sobotka

Svobodová

et al. 2011

Drug and Chemical Toxicology

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Oxime reactivator HI-6 (asoxime, in some sources) is a potent antidote suitable for treatment of intoxication by nerve agents. Despite the fact that HI-6 is considered for practical application in emergency situations, the impact of HI-6 on patients' bodies has not been established yet. The present experiment was carried out in order to estimate whether HI-6 would be able to trigger or protect from oxidative stress in a BALB/c mice model. HI-6 was applied in doses ranging from 0.2 to 20% of LD₅₀. Ferric-reducing antioxidant power (FRAP), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and glutathione reductase (GR) were assayed in the blood, liver, kidney, and brain of treated animals. It was found that HI-6 does not increase GR or TBARS. On the contrary, TBARS levels in the brain and liver were found to be significantly decreased in HI-6-treated animals. Pertinent antioxidant properties of HI-6 were excluded by the FRAP method. Endogenous antioxidants were unchanged, with the exception of the kidney. Low-molecular-weight antioxidants assayed by the FRAP method were significantly decreased in kidneys of animals treated with HI-6. However, GSH partially recovered the loss of the other low-molecular-weight antioxidants and was significantly increased in the kidney of HI-6-exposed mice. HI-6 potential to produce nephropathy is hypothesized. The achieved conclusions were quite surprising and showed a complex impact of HI-6 on the body.

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Section: Discussionmentioning

confidence: 97%

Investigation of oxidative stress in blood, brain, kidney, and liver after oxime antidote HI-6 application in a mouse experimental model

Pohanka

Sobotka

Svobodová

et al. 2011

Drug and Chemical Toxicology

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“…HI-6 may have effects on GABA-ergic neurotransmission in the CNS (Melchers et al, 1994). Other possible mechanisms of action at targets in the nervous system have been suggested for oximes such as alteration of the release of neurotransmitters (Clement, 1979;Kloog et al, 1986), inhibition of acetylcholine release by HI-6 (Van Helden et al, 1998), inhibition of synthesis of neurotransmitters (Clement, 1979), interaction with pre-synaptic cholinergic nerve terminals (Aas, 1996), and interaction at post-synaptic receptors (Van Helden et al, 1996). It has been shown that both PAM-2 and HI-6 interact with the nicotinic receptor ion complex (Alkondon et al, 1988).…”

Section: Pyridinium Oximesmentioning

confidence: 99%

Medical Treatment of Poisoning with Organophosphates and Carbamates

Jokanović¹

2011

Anticholinesterase Pesticides

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“…Furthermore, oximes can have effects on various steps of the cholinergic transmission e.g. inhibition of ACh synthesis [8], alteration of ACh release from neurons [11], and interaction with pre-and postsynaptic receptors [12]. It is possible that these additional pharmacological effects could lead to new oxime targets and improve our knowledge of their effects in the whole organism [13].…”

Section: University Of Defence Faculty Of Militarymentioning

confidence: 99%

Oximes as Inhibitors of Acetylholinesterase - A Structure-Activity Relationship (Sar) Study

Šepsová¹,

Karasová²,

Zemek³

et al. 2011

Mil. Med. Sci. Lett.

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Acetylcholinesterase (AChE) reactivators (oximes) are generally used as antidotes in case of nerve agent poisoning. Because of their affinity to AChE, they may also act as weak inhibitors of AChE. Their inhibition potency against AChE was determined by an in vitro method based on the interaction between AChE and oxime reactivator in the concentration range 10-1 to 10-8 M. We used eel AChE for these assays. We found that AChE inhibition strongly depends on the oxime structure. The aim of the present study is to describe the structure-activity relationship (SAR) between oxime structure and inhibition of AChE. AChE reactivators tested include both monoquaternary and bisquaternary structures with the oxime group in different positions on the pyridine ring and with changes in the connecting linker in the case of the bisquaternary compounds. We found AChE inhibition to be highest in bisquaternary oximes that have a longer linker length and have the oxime group in the ortho position. Increased AChE inhibition in monoquaternary oximes was highest when the meta position was occupied by the oxime nucleophile. In addition, different substituents in the connecting chain (in case of bisquaternary oximes) modulated their inhibition potency.

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In vitro effects of toxogonin, HI-6 and HLö-7 on the release of [3H]acetylcholine from peripheral cholinergic nerves in rat airway smooth muscle

Cited by 13 publications

References 39 publications

Investigation of oxidative stress in blood, brain, kidney, and liver after oxime antidote HI-6 application in a mouse experimental model

Investigation of oxidative stress in blood, brain, kidney, and liver after oxime antidote HI-6 application in a mouse experimental model

Medical Treatment of Poisoning with Organophosphates and Carbamates

Oximes as Inhibitors of Acetylholinesterase - A Structure-Activity Relationship (Sar) Study

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