Author(s): Singh NS, Paul RK, Torjman MC, Wainer IW
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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. Published by Elsevier Ireland Ltd.
This article was published in Neurosci Lett
and referenced in Journal of Clinical & Experimental Pharmacology