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• W2092149047 abstract "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 μ M ) 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 μ M ) reversibly lowered neuronal steady‐state pHi by 0.19±0.07 pH units in the presence of extracellular CO 2 /HCO 3 − buffer. In the nominal absence of extracellular CO 2 /HCO 3 − or in Na + ‐free CO 2 /HCO 3 − ‐buffered solution, LEV had no effect on steady‐state pHi. Recovery of pHi subsequent to ammonium prepulses remained unchanged in the absence of CO 2 /HCO 3 − buffer, but was significantly reduced by LEV in the presence of CO 2 /HCO 3 − buffer. These findings show that LEV inhibits HCO 3 − ‐dependent acid extrusion, but has no effect on Na + /H + exchange. LEV did not affect Na + ‐independent Cl − /HCO 3 − exchange because intracellular alkalosis upon withdrawal of extracellular Cl − remained unchanged. These data show that LEV at clinically relevant concentrations inhibits Na + ‐dependent Cl − /HCO 3 − exchange, lowers neuronal pHi, and thereby may contribute to its anticonvulsive activity. British Journal of Pharmacology (2004) 142 , 1073–1080. doi: 10.1038/sj.bjp.0705836" @default.
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• W2092149047 date "2004-08-01" @default.
• W2092149047 modified "2023-10-14" @default.
• W2092149047 title "Levetiracetam inhibits Na⁺-dependent Cl⁻/HCO₃⁻exchange of adult hippocampal CA3 neurons from guinea-pigs" @default.
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• W2092149047 doi "https://doi.org/10.1038/sj.bjp.0705836" @default.
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