An approved antiepileptic drug
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
参考文献:
[1]. Pan CF, et al. Inhibitory mechanisms of gabapentin, an antiseizure drug, on platelet aggregation. J Pharm Pharmacol. 2007 Sep;59(9):1255-61.
[2]. Gee NS, et al. The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. J Biol Chem. 1996 Mar 8;271(10):5768-76.
[3]. Abdel-Salam OM, et al. The effect of gabapentin on oxidative stress in a model of toxic demyelination in rat brain. J Basic Clin Physiol Pharmacol. 2012;23(2):61-8.
[4]. Yang JL, et al. Gabapentin reduces CX3CL1 signaling and blocks spinal microglial activation in monoarthritic rats. Mol Brain. 2012 May 30;5:18.
[5]. Zand L, et al. Gabapentin toxicity in patients with chronic kidney disease: a preventable cause of morbidity. Am J Med. 2010 Apr;123(4):367-73.
[6]. Hung TY, et al. Gabapentin toxicity: an important cause of altered consciousness in patients with uraemia. BMJ Case Rep. 2009;2009. pii: bcr11.2008.1268.
| Cell experiment [1]: | |
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Cell lines |
Pyramidal neocortical cells |
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Preparation method |
Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
10 μM |
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Applications |
Gabapentin inhibited calcium currents in pyramidal neocortical cells (up to 34%). The gabapentin-mediated inhibition of calcium currents saturated at particularly low concentrations (around 10 μM), at least in neocortical neurons (IC50 about 4 microM) |
| Animal experiment [1,2]: | |
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Animal models |
Rat model of neuropathic pain dynamic allodynia, rat model of brain demyelination evoked by intracerebral injection (i.c.i) of ethidium bromide |
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Dosage form |
Oral administration, 10-100 mg/kg |
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Application |
In the rat model of neuropathic pain dynamic allodynia, gabapentin (10-100 mg/kg, p.o.) dose-dependently blocked both types of allodynia. The intrathecal administration of gabapentin dose-dependently (1-100 μg/animal) blocked both static and dynamic allodynia. Administration of similar doses of gabapentin into the hind paw failed to block these responses. In a rat model of brain demyelination evoked by intracerebral injection (i.c.i) of ethidium bromide, gabapentin administered at 300 mg/kg increased cortical MDA by 66%. Gabapentin decreased GPx activity by 54.3%. Gabapentin decreased nitrite by 21.4% and 29.2% at 100 and 300 mg/kg, respectively. Gabapentin increased AChE activity increased by 28.6% and 69.3% at 100 and 300 mg/kg, respectively. Gabapentin decreased paraoxonase activity by 83.3% and 73% at 100 and 300 mg/kg, respectively. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1]. Abdel-Salam O M E, Khadrawy Y A, Mohammed N A, et al. The effect of gabapentin on oxidative stress in a model of toxic demyelination in rat brain[J]. 2012. [2]. Field M J, McCleary S, Hughes J, et al. Gabapentin and pregabalin, but not morphine and amitriptyline, block both static and dynamic components of mechanical allodynia induced by streptozocin in the rat[J]. Pain, 1999, 80(1): 391-398. | |
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