Document Detail

Levetiracetam inhibits Na+-dependent Cl-/HCO3- exchange of adult hippocampal CA3 neurons from guinea-pigs.
MedLine Citation:
PMID:  15249428     Owner:  NLM     Status:  MEDLINE    
The novel anticonvulsant levetiracetam (LEV) was tested for effects on bioelectric activity and intracellular pH (pHi) regulation of hippocampal CA3 neurons from adult guinea-pigs. In 4-aminopyridine-treated slices, LEV (10-100 microm) reduced the frequency of action potentials and epileptiform bursts of CA3 neurons by 30-55%, while the shape of these potentials remained largely unchanged. Suppressive effects were reversed by an increase of pHi with trimethylamine (TMA). Using BCECF-AM-loaded slices, we found that LEV (10-50 microm) reversibly lowered neuronal steady-state pHi by 0.19 +/- 0.07 pH units in the presence of extracellular CO2/HCO3- buffer. In the nominal absence of extracellular CO2/HCO3- or in Na+-free CO2/HCO3(-)-buffered solution, LEV had no effect on steady-state pHi. Recovery of pHi subsequent to ammonium prepulses remained unchanged in the absence of CO2/HCO3- buffer, but was significantly reduced by LEV in the presence of CO2/HCO3- buffer. These findings show that LEV inhibits HCO3(-)-dependent acid extrusion, but has no effect on Na+/H+ exchange. LEV did not affect Na+-independent Cl-/HCO3- exchange because intracellular alkalosis upon withdrawal of extracellular Cl- remained unchanged. These data show that LEV at clinically relevant concentrations inhibits Na+-dependent Cl-/HCO3- exchange, lowers neuronal pHi, and thereby may contribute to its anticonvulsive activity.
Tobias Leniger; Jan Thöne; Udo Bonnet; Andreas Hufnagel; Dieter Bingmann; Martin Wiemann
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Publication Detail:
Type:  In Vitro; Journal Article     Date:  2004-07-12
Journal Detail:
Title:  British journal of pharmacology     Volume:  142     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-07-30     Completed Date:  2005-08-04     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1073-80     Citation Subset:  IM    
Copyright Information:
Copyright 2004 Nature Publishing Group
Department of Neurology, University of Essen, Hufelandstr. 55, Essen 45122, Germany.
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MeSH Terms
Action Potentials
Anticonvulsants / pharmacology*
Cations, Monovalent
Chloride-Bicarbonate Antiporters / antagonists & inhibitors*
Guinea Pigs
Hippocampus / cytology,  drug effects*,  physiology
Hydrogen-Ion Concentration
Neurons / drug effects*,  physiology
Piracetam / analogs & derivatives*,  pharmacology*
Sodium / metabolism*
Time Factors
Reg. No./Substance:
0/Anticonvulsants; 0/Buffers; 0/Cations, Monovalent; 0/Chloride-Bicarbonate Antiporters; 230447L0GL/etiracetam; 7440-23-5/Sodium; 7491-74-9/Piracetam

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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