Linked Life Data

19111886

Source:http://linkedlifedata.com/resource/pubmed/id/19111886

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-1-26
pubmed:abstractText
Organophosphate (OP)-nerve agent poisoning may lead to prolonged epileptiform seizure activity, which can result in irreversible neuronal brain damage. A timely and effective control of seizures with pharmacological agents can minimize the secondary and long-term neuropathology that may result from this damage. Diazepam, the current anticonvulsant of choice in the management of OP poisoning, is associated with unwanted effects such as sedation, amnesia, cardio-respiratory depression, anticonvulsant tolerance, and dependence liabilities. In search for an efficacious and safer anticonvulsant benzodiazepine, we studied imidazenil, a potent anticonvulsant that is devoid of sedative action and has a low intrinsic efficacy at alpha1- but is a high efficacy positive allosteric modulator at alpha5-containing GABA(A) receptors. We compared the potency of a combination of 2 mg/kg, i.p. atropine with: (a) imidazenil 0.05-0.5 mg/kg i.p. or (b) equipotent anti-bicuculline doses of diazepam (0.5-5 mg/kg, i.p.), against diisopropyl fluorophosphate (DFP; 1.5 mg/kg, s.c.)-induced status epilepticus and its associated neuronal damage. The severity and frequency of seizure activities were determined by continuous radio telemetry recordings while the extent of neuronal damage and neuronal degeneration were assessed using the TUNEL-based cleaved DNA end-labeling technique or neuron-specific nuclear protein (NeuN)-immunolabeling and Fluoro-Jade B (FJB) staining, respectively. We report here that the combination of atropine and imidazenil is at least 10-fold more potent and longer lasting than the combination with diazepam at protecting rats from DFP-induced seizures and the associated neuronal damage or ongoing degeneration in the anterior cingulate cortex, CA1 hippocampus, and dentate gyrus. While 0.5 mg/kg imidazenil effectively attenuated DFP-induced neuronal damage and the ongoing neuronal degeneration in the anterior cingulate cortex, dentate gyrus, and CA1 hippocampus, 5 mg/kg or a higher dose of diazepam is required to produce similar protective effects. These finding suggests that imidazenil, a non-sedating anticonvulsant BZ ligand, is a more potent, effective, and safer drug than diazepam in protecting rats from DFP-induced seizures and the associated neuronal damage and/or ongoing neuronal degeneration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0300-483X
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
256
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
164-74
pubmed:meshHeading
pubmed-meshheading:19111886-Animals, pubmed-meshheading:19111886-Anticonvulsants, pubmed-meshheading:19111886-Behavior, Animal, pubmed-meshheading:19111886-Benzodiazepines, pubmed-meshheading:19111886-Brain, pubmed-meshheading:19111886-Cholinesterase Inhibitors, pubmed-meshheading:19111886-DNA Fragmentation, pubmed-meshheading:19111886-Diazepam, pubmed-meshheading:19111886-Electroencephalography, pubmed-meshheading:19111886-Imidazoles, pubmed-meshheading:19111886-In Situ Nick-End Labeling, pubmed-meshheading:19111886-Isoflurophate, pubmed-meshheading:19111886-Male, pubmed-meshheading:19111886-Neurons, pubmed-meshheading:19111886-Rats, pubmed-meshheading:19111886-Rats, Inbred F344, pubmed-meshheading:19111886-Seizures, pubmed-meshheading:19111886-Status Epilepticus, pubmed-meshheading:19111886-Telemetry
pubmed:year
2009
pubmed:articleTitle
Imidazenil, a non-sedating anticonvulsant benzodiazepine, is more potent than diazepam in protecting against DFP-induced seizures and neuronal damage.
pubmed:affiliation
The Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL 60612, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't