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Gabapentin and (S)-pregabalin decrease intracellular D-serine concentrations in PC-12 cells.

Abstract
The effects of gabapentin (GBP) and (S)-pregabalin (PGB) on the intracellular concentrations of d-serine and the expression of serine racemase (SR) in PC-12 cells were determined. Intracellular d-serine concentrations were determined using an enantioselective capillary electrophoresis assay with laser-induced fluorescence detection. Increasing concentrations of GBP, 0.1-20μM, produced a significant decrease in d-serine concentration relative to control, 22.9±6.7% at 20μM (*p<0.05), with an IC(50) value of 3.40±0.29μM. Increasing concentrations of PGB, 0.1-10μM, produced a significant decrease in d-serine concentration relative to control, 25.3±7.6% at 10μM (*p<0.05), with an IC(50) value of 3.38±0.21μM. The compounds had no effect on the expression of monomeric-SR or dimeric-SR as determined by Western blotting. The results suggest that incubation of PC-12 cells with GBP and PGB reduced the basal activity of SR, which is most likely a result of the decreased Ca(2+) flux produced via interaction of the drugs with the α(2)-δ subunit of voltage-gated calcium channels. d-Serine is a co-agonist of the N-methyl d-aspartate receptor (NMDAR) and reduced d-serine concentrations have been associated with reduced NMDAR activity. Thus, GBP and PGB may act as indirect antagonists of NMDAR, a mechanism that may contribute to the clinical effects of the drugs in neuropathic pain.
AuthorsNagendra S Singh, Rajib K Paul, Marc C Torjman, Irving W Wainer
JournalNeuroscience letters (Neurosci Lett) Vol. 535 Pg. 90-4 (Feb 22 2013) ISSN: 1872-7972 [Electronic] Ireland
PMID23274708 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
CopyrightPublished by Elsevier Ireland Ltd.
Chemical References
  • Amines
  • Analgesics
  • Cyclohexanecarboxylic Acids
  • Serine
  • Pregabalin
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Racemases and Epimerases
  • serine racemase
Topics
  • Amines (pharmacology)
  • Analgesics (pharmacology)
  • Animals
  • Cyclohexanecarboxylic Acids (pharmacology)
  • Gabapentin
  • Intracellular Space (metabolism)
  • PC12 Cells
  • Pregabalin
  • Racemases and Epimerases (metabolism)
  • Rats
  • Serine (chemistry, metabolism)
  • Stereoisomerism
  • gamma-Aminobutyric Acid (analogs & derivatives, chemistry, pharmacology)

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