Age- and dose-specific anticonvulsant action of bumetanide in immature rats.
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.
Mares
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Institute of Physiology ASCR, Prague, Czech Republic. maresp@biomed.cas.cz
D000367:Age Factors; D000375:Aging; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002034:Bumetanide / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology*; D028021:Sodium-Potassium-Chloride Symporters / Q000187:drug effects* / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; C578879:Slc12a2 protein, rat; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide; D005680:gamma-Aminobutyric Acid; D010433:Pentylenetetrazole