Gabapentin (Neurontin) is a pharmaceutical drug, specifically a GABA analog. It was originally developed to treat epilepsy, and currently is also used to relieve neuropathic pain.IC50 Value: 140 nM (α2δ subunit of calcium channel) [1]Target: Calcium Channelin vitro: Gabapentin, baclofen and CGP 44532 all reduced the electrically stimulated release of [3H]glutamic acid (IC50=20 microM, 0.8 microM and 2 microM, respectively). Gabapentin was without effect on the release of [3H]GABA, whilst baclofen (IC50=8 microM) and CGP 44532 (IC50=1 microM) inhibited [3H]GABA release [2]. A large inhibition of calcium currents by gabapentin was observed in pyramidal neocortical cells (up to 34%). Significantly, the gabapentin-mediated inhibition of calcium currents saturated at particularly low concentrations (around 10 microM), at least in neocortical neurons (IC50 about 4 microM) [3].in vivo: Gabapentin produced an anti-allodynic effect over the 7-day period, reducing the expression of pro-inflammatory cytokines but increasing the expression of IL-10 (TNF-α, 316.0 ± 69.7 pg/mL vs 88.8 ± 24.4 pg/mL; IL-1β, 1,212.9 ± 104.5 vs 577.4 ± 97.1 pg/mL; IL-6, 254.0 ± 64.8 pg/mL vs 125.5 ± 44.1 pg/mL; IL-10, 532.1 ± 78.7 pg/mL vs 918.9 ± 63.1 pg/mL). The suppressive effect of gabapentin on pro-inflammatory cytokine expression was partially blocked by the anti-IL-10 antibody [4].Toxicity: No new safety signals or adverse event trends relating to GEn exposure were identified [5].Clinical trial: N/A
References:
[1]. Receveur JM, et al. Synthesis and biological evaluation of conformationally restricted Gabapentin analogues. Bioorg Med Chem Lett. 1999 Aug 16;9(16):2329-34.
[2]. Parker DA, et al. Gabapentin activates presynaptic GABAB heteroreceptors in rat cortical slices. Eur J Pharmacol. 2004 Jul 14;495(2-3):137-43.
[3]. Stefani A, et al. Gabapentin inhibits calcium currents in isolated rat brain neurons. Neuropharmacology. 1998;37(1):83-91.
[4]. Lee BS, et al. Intrathecal gabapentin increases interleukin-10 expression and inhibits pro-inflammatory cytokine in a rat model of neuropathic pain. J Korean Med Sci. 2013 Feb;28(2):308-14.
[5]. Harden RN, et al. A Phase 2a, Randomized, Crossover Trial of Gabapentin Enacarbil for the Treatment of Postherpetic Neuralgia inGabapentin Inadequate Responders. Pain Med. 2013 Sep 18.