Protective effects of S(+) ketamine and atropine against lethality and brain damage during soman-induced status epilepticus in guinea-pigs

Dorandeu, Frédéric; Baille, Valérie; Mikler, John; Testylier, Guy; Lallement, G.; Sawyer, Thomas W.; Carpentier, Pierre

doi:10.1016/j.tox.2007.02.012

Cited by 40 publications

(25 citation statements)

References 33 publications

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“…If we attempt to make a very rough estimate based on the blood concentrations of caramiphen after repeated or continuous administration (Levandoski and Flanagan, 1980; Levy et al ., 2007), we would suggest that a single injection of 100 mg·kg −1 caramiphen produced a blood concentration in the micromolar range. It is likely, therefore, that the NMDA receptor‐antagonistic properties of caramiphen contributed to its anticonvulsant efficacy; previous studies have suggested that antagonism of NMDA receptors plays an important role in the termination of nerve agent‐induced seizures (Braitman and Sparenborg, 1989; Dorandeu et al ., 2007). Regardless, however, of the extent of similarity between the in vitro and the in vivo caramiphen concentrations in the present study, the finding that caramiphen antagonizes NMDA receptor activation in a structure like the BLA, is likely to have significant implications in understanding the anticonvulsant mechanisms of this compound, as the BLA plays a central role in seizure generation and propagation (Aroniadou‐Anderjaska et al ., 2008), including seizures induced by nerve agents (McDonough et al ., 1987; Apland et al ., 2009; Aroniadou‐Anderjaska et al ., 2009; Skovira et al ., 2010).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective efficacy of caramiphen against soman and mechanisms of its action

Figueiredo

Aroniadou‐Anderjaska

Qashu

et al. 2011

British Journal of Pharmacology

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BACKGROUND AND PURPOSECaramiphen is a muscarinic antagonist with potent anticonvulsant properties. Here, we investigated the efficacy of caramiphen against behavioural seizures and neuropathology induced by the nerve agent soman, and revealed two mechanisms that may underlie the anticonvulsant efficacy of caramiphen. EXPERIMENTAL APPROACHRats were given caramiphen at 30 or 60 min after treatment with soman. Neuronal loss in the basolateral amygdala (BLA) and neuronal degeneration in the amygdala, hippocampus, piriform cortex, entorhinal cortex and neocortex, were investigated 24 h after soman, using design-based stereology and FluoroJade-C staining. The effects of caramiphen on NMDA-, AMPA-and GABA-evoked currents were studied in the BLA region of in vitro brain slices from un-treated rats, using whole-cell recordings. KEY RESULTSCaramiphen given either 30 min or 60 min after soman, suppressed behavioural seizures within 10 min, but required 1~4.5 h for complete cessation of seizures. Neuronal loss and degeneration were significantly reduced in the caramiphen-treated, soman-exposed rats. Postsynaptic currents evoked by puff-application of NMDA on BLA principal cells were reduced by caramiphen in a dose-dependent manner (100 mM, 300 mM and 1 mM), while GABA-evoked currents were facilitated by 100 mM and 300 mM, but depressed by 1 mM caramiphen. AMPA-evoked currents were not affected by caramiphen. CONCLUSIONS AND IMPLICATIONSCaramiphen offered partial protection against soman-induced seizures and neuropathology, even when given 60 min after soman. NMDA receptor antagonism and facilitation of GABAergic inhibition in the BLA may play a key role in the anticonvulsive and neuroprotective properties of caramiphen.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective efficacy of caramiphen against soman and mechanisms of its action

Figueiredo

Aroniadou‐Anderjaska

Qashu

et al. 2011

British Journal of Pharmacology

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“…Ketamine in combination with atropine, with or without a benzodiazepine, appears to have utility in reducing the effects of organophosphorus nerve agents including soman, which could have utility in field conditions [171]. A study in guinea pigs exposed to soman showed that (S)ketamine and atropine provided comparable protection against death and seizure-related brain damage, but at doses 2-3 times lower than racemic ketamine and atropine [172].…”

Section: Seizuresmentioning

confidence: 99%

A Review of Nonanesthetic Uses of Ketamine

Pribish

Wood

Kalava

2020

Anesthesiology Research and Practice

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Ketamine, a nonselective NMDA receptor antagonist, is used widely in medicine as an anesthetic agent. However, ketamine’s mechanisms of action lead to widespread physiological effects, some of which are now coming to the forefront of research for the treatment of diverse medical disorders. This paper aims at reviewing recent data on key nonanesthetic uses of ketamine in the current literature. MEDLINE, CINAHL, and Google Scholar databases were queried to find articles related to ketamine in the treatment of depression, pain syndromes including acute pain, chronic pain, and headache, neurologic applications including neuroprotection and seizures, and alcohol and substance use disorders. It can be concluded that ketamine has a potential role in the treatment of all of these conditions. However, research in this area is still in its early stages, and larger studies are required to evaluate ketamine’s efficacy for nonanesthetic purposes in the general population.

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“…Stoga je u našem eksperimentu, indirektno, preko ekstravazacije boje, semikvantitativno ispitivan antikonvulzivni potencijal memantina i upoređen sa istim efektom midazolama i ketamina. Iako su i memantin i ketamin nekompetitivni antagonisti NMDA receptora, za razliku od memantina, ketamin je bio neefikasan 43,69 . Midazolam je bio gotovo podjednako efikasan kao i memantin.…”

Section: Diskusijaunclassified

Antidotal effect of combinations obidoxime/HI-6 and memantine in mice poisoned with soman, dichlorvos or heptenophos

Antonijević¹,

Stojiljković

Bokonjić³

et al. 2011

VOJNOSANIT PREGL

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Protective effects of S(+) ketamine and atropine against lethality and brain damage during soman-induced status epilepticus in guinea-pigs

Cited by 40 publications

References 33 publications

Neuroprotective efficacy of caramiphen against soman and mechanisms of its action

Neuroprotective efficacy of caramiphen against soman and mechanisms of its action

A Review of Nonanesthetic Uses of Ketamine

Antidotal effect of combinations obidoxime/HI-6 and memantine in mice poisoned with soman, dichlorvos or heptenophos

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