The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

Schultz, Mark; Wright, Linnzi; Stone, Michael; Schwartz, J.E.; Kelley, N.R.; Moffett, Mark C.; Lee, R.B.; Lumley, Lucille A.

doi:10.1016/j.taap.2012.01.017

Cited by 30 publications

(41 citation statements)

References 49 publications

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“…Caramiphen treatment as adjunct to standard therapy following onset of GD-induced SE dose-dependently reduced seizure activity, attenuated deficits in spatial memory and fear conditioning, and protected against the development of severe neuronal degeneration. Previously, we observed in a short-term (72 h) study that caramiphen (20 mg/kg, im) in combination with diazepam (10 mg/kg, sc) reduces seizure duration and neuronal degeneration following GD exposure when treatment is delayed 30 min after seizure onset (Schultz et al, 2012). Our present findings expand on those findings to demonstrate that caramiphen as adjunct to standard therapy dose-dependently attenuated the development of GD-induced cognitive impairment in the month following exposure.…”

Section: Discussionmentioning

confidence: 98%

“…Caramiphen is an effective anticonvulsant when administered within 10 min after GD-induced seizure onset (Schultz et al, 2012). However, when administered at delayed time points of 20 or 30 min after seizure onset, caramiphen (20 mg/kg, im) in combination with diazepam (10 mg/kg, sc) treatment is needed to reduce seizure duration and neuropathological damage following GD exposure (Schultz et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Caramiphen edisylate is an anticholinergic drug with antiglutamatergic properties and has anticonvulsant effects against nerve agent in rats Neurotoxicology and Teratology 44 (2014) 89-104 (Figueiredo et al, 2011;Schultz et al, 2012). Caramiphen displaces [ 3 H]-pirenzepine and [ 3 H]-quinuclidinyl benzilate from M1 and M2 muscarinic receptors, respectively (Hudkins and DeHaven-Hudkins, 1991;Hudkins et al, 1993), and inhibits nicotine-induced tremors (Gao et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Caramiphen treatment administered 5 or 10 min after GD exposure blocks EEG seizure activity in rats (Raveh et al, 2003;Schultz et al, 2012). Caramiphen treatment in the absence of diazepam 5, 10 or 20 min after the onset of sarin-induced convulsions reduces signs of toxicity, spatial memory impairment in the Morris water maze, and neuroinflammatory response (5 and 10 min treatment only; Raveh et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Caramiphen treatment in the absence of diazepam 5, 10 or 20 min after the onset of sarin-induced convulsions reduces signs of toxicity, spatial memory impairment in the Morris water maze, and neuroinflammatory response (5 and 10 min treatment only; Raveh et al, 2008). At delayed time points (20 or 30 min) following GD-induced seizure onset, caramiphen is less effective as an anticonvulsant than when used in combination with diazepam (Schultz et al, 2012). The goal of the present study is to investigate the use of caramiphen as an adjunct treatment to standard therapy to prevent or ameliorate behavioral deficits that follow GD exposure in rats.…”

Section: Introductionmentioning

confidence: 99%

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Caramiphen edisylate as adjunct to standard therapy attenuates soman-induced seizures and cognitive deficits in rats

Schultz¹,

Wright²,

Furtado

et al. 2014

Neurotoxicology and Teratology

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Caramiphen edisylate as adjunct to standard therapy attenuates soman-induced seizures and cognitive deficits in rats

Schultz¹,

Wright²,

Furtado

et al. 2014

Neurotoxicology and Teratology

Self Cite

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Neurosteroid and benzodiazepine combination therapy reduces status epilepticus and long‐term effects of whole‐body sarin exposure in rats

Lumley¹,

Miller

Muse

et al. 2019

Epilepsia Open

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Objective Our objective was to evaluate the protective efficacy of the neurosteroid pregnanolone (3α‐hydroxy‐5β pregnan‐20‐one), a GABA A receptor‐positive allosteric modulator, as an adjunct to benzodiazepine therapy against the chemical warfare nerve agent (CWNA) sarin (GB), using whole‐body exposure, an operationally relevant route of exposure to volatile GB. Methods Rats implanted with telemetry transmitters for the continuous measurement of cortical electroencephalographic (EEG) activity were exposed for 60 minutes to 3.0 LCt 50 of GB via whole‐body exposure. At the onset of toxic signs, rats were administered an intramuscular injection of atropine sulfate (2 mg/kg) and the oxime HI‐6 (93.6 mg/kg) to increase survival rate and, 30 minutes after seizure onset, treated subcutaneously with diazepam (10 mg/kg) and intravenously with pregnanolone (4 mg/kg) or vehicle. Animals were evaluated for GB‐induced status epilepticus (SE), spontaneous recurrent seizures (SRS), impairment in spatial memory acquisition, and brain pathology, and treatment groups were compared. Results Delayed dual therapy with pregnanolone and diazepam reduced time in SE in GB‐exposed rats compared to those treated with delayed diazepam monotherapy. The combination therapy of pregnanolone with diazepam also prevented impairment in the Morris water maze and reduced the neuronal loss and neuronal degeneration, evaluated at one and three months after exposure. Significance Neurosteroid administration as an adjunct to benzodiazepine therapy offers an effective means to treat benzodiazepine‐refractory SE, such as occurs following delayed treatment of GB exposure. This study is the first to present data on the efficacy of delayed pregnanolone and diazepam dual therapy in reducing seizure activity, performance deficits and brain pathology following an operationally relevant route of exposure to GB and supports the use of a neurosteroid as an adjunct to standard anticonvulsant therapy for the treatment of CWNA‐induced SE.

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Combination of antiseizure medications phenobarbital, ketamine, and midazolam reduces soman‐induced epileptogenesis and brain pathology in rats

et al. 2021

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The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

Cited by 30 publications

References 49 publications

Caramiphen edisylate as adjunct to standard therapy attenuates soman-induced seizures and cognitive deficits in rats

Caramiphen edisylate as adjunct to standard therapy attenuates soman-induced seizures and cognitive deficits in rats

Neurosteroid and benzodiazepine combination therapy reduces status epilepticus and long‐term effects of whole‐body sarin exposure in rats

Combination of antiseizure medications phenobarbital, ketamine, and midazolam reduces soman‐induced epileptogenesis and brain pathology in rats

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