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.
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Authors | Nagendra S Singh, Rajib K Paul, Marc C Torjman, Irving W Wainer |
Journal | Neuroscience letters
(Neurosci Lett)
Vol. 535
Pg. 90-4
(Feb 22 2013)
ISSN: 1872-7972 [Electronic] Ireland |
PMID | 23274708
(Publication Type: Journal Article, Research Support, N.I.H., Intramural)
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Copyright | Published by Elsevier Ireland Ltd. |
Chemical References |
- Amines
- Analgesics
- Cyclohexanecarboxylic Acids
- Serine
- Pregabalin
- gamma-Aminobutyric Acid
- Gabapentin
- Racemases and Epimerases
- serine racemase
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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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