Age- and dose-specific anticonvulsant action of bumetanide in immature rats
Language English Country Czech Republic Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
20059292
DOI
10.33549/physiolres.931897
PII: 931897
Knihovny.cz E-resources
- MeSH
- Anticonvulsants pharmacology MeSH
- Bumetanide pharmacology MeSH
- Epilepsy, Tonic-Clonic chemically induced metabolism prevention & control MeSH
- gamma-Aminobutyric Acid metabolism MeSH
- Sodium Potassium Chloride Symporter Inhibitors pharmacology MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Pentylenetetrazole MeSH
- Rats, Wistar MeSH
- Reaction Time MeSH
- Solute Carrier Family 12, Member 2 MeSH
- Sodium-Potassium-Chloride Symporters drug effects metabolism MeSH
- Aging MeSH
- Age Factors MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Anticonvulsants MeSH
- Bumetanide MeSH
- gamma-Aminobutyric Acid MeSH
- Sodium Potassium Chloride Symporter Inhibitors MeSH
- Pentylenetetrazole MeSH
- Solute Carrier Family 12, Member 2 MeSH
- Slc12a2 protein, rat MeSH Browser
- Sodium-Potassium-Chloride Symporters MeSH
GABA exhibits depolarizing action in the immature neurons due to high intracellular activity of chloride ions. It is maintained by cation-chloride cotransporter NKCC1 which is present in immature brain. Bumetanide is a specific inhibitor of this cotransporter. We studied possible anticonvulsant activity of bumetanide in pentylenetetrazol-induced seizures in three age groups of rat pups (7, 12, and 18 days old). Pretreatment with bumetanide (0.2-1 mg/kg i.p.) resulted in dose-dependent decrease of incidence of the tonic phase of generalized tonic-clonic seizures in 12-day-old rats only. No effect was observed in younger and older animals. Higher dose of bumetanide (2.5 mg/kg) did not affect tonic convulsions but, on the contrary, decreased latencies of generalized seizures in 12-day-old animals. Lack of marked anticonvulsant effect is probably due to relative maturity of neurons in the brainstem where the generator of generalized seizures is localized. Age- and dose-specific suppression of the tonic phase needs further analysis.
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