Protection against soman-induced seizures in rats: relationship among doses of prophylactics, soman, and adjuncts

Myhrer, Trond; Nguyen, Nga H.T.; Andersen, Jannike Mørch; Aas, Pål

doi:10.1016/j.taap.2004.01.007

Cited by 35 publications

(15 citation statements)

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“…Incapacitation is most likely related to elevated brain levels of acetylcholine [25]. In the present study, the rats were incapacitated for nearly 2 h, whereas rats pretreated systemically (physostigmine and procyclidine) are only incapacitated for about 1/2 h following exposure to soman [4]. This difference in response to prophylactic treatments is probably associated with lack of anticholinergic influence beyond the confined area of AT in the present animals.…”

Section: Cholinergic and Glutamatergic Antagonismmentioning

confidence: 47%

“…Procyclidine and caramiphen exert cholinergic antagonism at both muscarinic and nicotinic receptors [7,30,31]. Furthermore, procyclidine inhibits the phencyclidine site at the NMDA receptor very potently [32] in a concentration-dependent manner [4], whereas caramiphen appears to bind to the Zn 2+ site at the NMDA receptor [33] and additionally has blocking effect on the AMPA receptor [9]. Procyclidine and caramiphen differ in their capabilities to antagonize a lethal dose of NMDA in mice.…”

Section: Pharmacological Properties Of Procyclidine and Caramiphenmentioning

confidence: 99%

“…Both treatment regimens can effectively terminate somaninduced seizures in rats when administered 30 min after onset [2,3]. Procyclidine exerts antagonism at both muscarinic and nicotinic receptors and additionally has antagonistic effect at NMDA receptors [4], whereas diazepam and pentobarbital enhance GABA A neurotransmission [1]. Propofol has both GABAergic agonism and antagonistic NMDA effects [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…Propofol has both GABAergic agonism and antagonistic NMDA effects [5,6]. Procyclidine (1-6 mg/kg) has also been shown to cause efficient prophylactic protection against soman-evoked seizures when coadministered with physostigmine (0.1 mg/kg) to rats [4].…”

Section: Introductionmentioning

confidence: 99%

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Anticonvulsant Efficacy of Drugs with Cholinergic and/or Glutamatergic Antagonism Microinfused into Area Tempestas of Rats Exposed to Soman

2007

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A group of antiparkinson drugs (benactyzine, biperiden, caramiphen, procyclidine, and trihexyphenidyl) has been shown to possess both anticholinergic and antiglutamatergic properties, making these agents very well suited as anticonvulsants against nerve agents. The first purpose of this study was to make a comparative assessment of the anticonvulsant potencies of the antiparkinson agents when microinfused (1 microl) into the seizure controlling area tempestas (AT) of rats 20 min before subcutaneous injection of soman (100 microg/kg). The second purpose was to determine whether cholinergic and/or glutamatergic antagonism was the effective property. The results showed that only procyclidine (6 microg) and caramiphen (10 microg) antagonized soman-induced seizures. Cholinergic, and not glutamatergic, antagonism was likely the active property, since atropine (100 microg), and scopolamine (1 microg) caused anticonvulsant effects, whereas MK-801 (1 microg), and ketamine (50 microg) did not. Soman (11 nmol) injected into AT resulted more frequently in clonic convulsions than full tonic-clonic convulsions. AT may serve as both a trigger site for soman-evoked seizures and a site for screening anticonvulsant potencies of future countermeasures.

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Section: Cholinergic and Glutamatergic Antagonismmentioning

confidence: 47%

Section: Pharmacological Properties Of Procyclidine and Caramiphenmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anticonvulsant Efficacy of Drugs with Cholinergic and/or Glutamatergic Antagonism Microinfused into Area Tempestas of Rats Exposed to Soman

2007

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“…Other systems may, in addition or independently, be involved in OPs intoxicatin. 20,21) Since the alterations of GABAergic system on OPs pesticides intoxication process remains obscured, more remedial approaches are needed to understand the GABAergic mechanisms involved in OPs intoxication. The present paper investigates the alterations of GABAergic system in rat cortex consequent to acute and subchronic dimethoate administration to explore the role of the IAA system in OPs poisoning.…”

Section: Introductionmentioning

confidence: 99%

Effects of Acute and Subchronic Exposures to Dimethoate on Rat Cerebral Cortex GABAergic System

Ban

Chang

et al. 2010

JOURNAL OF HEALTH SCIENCE

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The effects of acute and subchronic administration of dimethoate on γ-aminobutyric (GABA) concentration and receptor characteristics in rat cerebral cortices were investigated. After a single (acute exposure) or repeated administration of dimethoate, rat cerebral cortex was found to inhibit acetylcholinesterase (AChE) activity in a dosedependent manner. No significant alteration in the concentration of GABA or the numbers of GABA A receptor was noted in cortices of rats after acute exposure to dimethoate except the affinities of the receptor was found elevated significantly following the acute administration. But the GABA concentrations were significantly reduced in the 10 and 20 mg/kg groups after the subchronic dimethoate administration. No difference was found statistically in the GABA A receptor binding in cortices after the subchronic administration of dimethoate. But the K d values were significant decreased reflecting an elevated affinity of receptors in the three dimethoate groups as compared with that of control follow subchronic administration. It is suggested that the GABAergic system is involved in the intoxication of the dimethoate intoxication which is probably to counteract the enhanced cholinergic activity induced by dimethoate.

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Determination of anti‐convulsant and life‐preserving capacities of three types of auto‐injector therapies against soman intoxication in rats

Myhrer

Enger

Aas

2012

Drug Testing and Analysis

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More effective countermeasures against nerve-agent poisoning are needed, because current ones do not protect sufficiently, particularly the central nervous system (CNS). The purpose of the present study was to make a comparison of the antidotal capabilities of atropine/obidoxime/diazepam (termed the obidoxime regimen), atropine/HI-6 (1-[([4-(aminocarbonyl)pyridinio]methoxy)methyl]-2-[(hydroxyimino)methyl]pyridinium)/avizafone (termed the HI-6 regimen), and scopolamine/HI-6/physostigmine (termed the physostigmine regimen) against various doses of soman (2, 3, 4 x LD50 ). The results showed that each regimen administered twice (1 min and 5 min after exposure) effectively prevented or terminated epileptiform activity within 10 min. However, the regimens differed markedly in life-saving properties with the physostigmine regimen ranking highest followed in descending order by the HI-6 and obidoxime regimens. Pretreatment with pyridostigmine increased the potency of the HI-6 regimen, but not the obidoxime regimen. The latter regimen administered thrice (1 min, 5 min, and 9 min after exposure) did not compensate for the insufficiency. In half of the rats that lived for 7 days, neuropathology was unexpectedly observed predominantly in the left hemisphere unrelated to whether they seized or not. Local glutamatergic excitotoxic activity may occur even if manifest toxic signs are absent. The physostigmine regimen has excellent antidotal capacity, but the very narrow therapeutic window (< 10 min) makes it unsuitable for use in the field. The HI-6 regimen appears to constitute an efficacious therapy against lower doses of soman (2 and 3 x LD50).

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Protection against soman-induced seizures in rats: relationship among doses of prophylactics, soman, and adjuncts

Cited by 35 publications

References 35 publications

Anticonvulsant Efficacy of Drugs with Cholinergic and/or Glutamatergic Antagonism Microinfused into Area Tempestas of Rats Exposed to Soman

Anticonvulsant Efficacy of Drugs with Cholinergic and/or Glutamatergic Antagonism Microinfused into Area Tempestas of Rats Exposed to Soman

Effects of Acute and Subchronic Exposures to Dimethoate on Rat Cerebral Cortex GABAergic System

Determination of anti‐convulsant and life‐preserving capacities of three types of auto‐injector therapies against soman intoxication in rats

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