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Chemical Compound Review

Aclonium     2-[1-(aminomethyl) cyclohexyl]ethanoic acid

Synonyms: Fanatrex, Gabarone, Neuontin, Gabapen, Gabapetin, ...
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Disease relevance of CI 945


Psychiatry related information on CI 945


High impact information on CI 945

  • Two-photon imaging of live exposed cortex showed that several antiepileptic agents, including valproate, gabapentin and phenytoin, reduced the ability of astrocytes to transmit Ca(2+) signaling [11].
  • Alternatively, AEDs may specifically target pathological channels; for example, gabapentin is a ligand of alpha2delta voltage-activated calcium channel subunits that are overexpressed in sensory neurons after nerve injury [12].
  • Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial [4].
  • By intent-to-treat analysis, subjects receiving gabapentin had a statistically significant reduction in average daily pain score from 6.3 to 4.2 points compared with a change from 6.5 to 6.0 points in subjects randomized to receive placebo (P<.001) [5].
  • In an anecdotal report, complete resolution of chemotherapy-induced nausea was seen in a patient with breast cancer, after she was placed on the anticonvulsant gabapentin [13].

Chemical compound and disease context of CI 945


Biological context of CI 945


Anatomical context of CI 945

  • Here we report that gabapentin is an agonist at the GABA(B) gb1a-gb2 heterodimer coupled to Kir 3.1/3.2 inwardly rectifying K+ channels in Xenopus laevis oocytes [23].
  • Gabapentin did not displace [(3)H]GABA from GABA(B) receptor sites in rat synaptic membranes [21].
  • Because of high levels of GABA(B(1a)) in the canine nodose ganglion, this finding indirectly supports the inactivity of gabapentin on the GABA(B(1a,2)) heterodimer demonstrated in various in vitro assays [21].
  • This case demonstrates the correspondence between rCBF and pain associated with spinal cord injury and also suggests the potential utility of gabapentin for treatment of this central pain state [24].
  • Gabapentin (GP) has been shown to have antihyperalgesic properties and the site of drug action is reported to be the central nervous system [25].

Associations of CI 945 with other chemical compounds

  • GABA was elevated in patients taking gabapentin compared with 14 complex partial epilepsy patients, matched for antiepileptic drug treatment [26].
  • EVIDENCE ACQUISITION: A MEDLINE search was conducted, limiting searching to double-blind, randomized, controlled trials (1978 to present) of antiepileptic drugs (carbamazepine, gabapentin, pregabalin, topiramate, and lamotrigine) used in the treatment of chronic neuropathic pain [27].
  • The NNT was 2.6 for tricyclic antidepressants, 6.7 for selective serotonin reuptake inhibitors, 2.5 for anticonvulsant sodium channel blockers, 4.1 for the anticonvulsant calcium channel blocker gabapentin, and 3.4 for the mixed opioid and monoaminergic drug tramadol, as calculated from a sufficiently large number of patients [28].
  • This controlled comparative study evaluated the efficacy of lamotrigine (LTG) and gabapentin (GBP) monotherapy versus placebo (PLC) [29].
  • Clinical pharmacokinetics of newer antiepileptic drugs. Lamotrigine, vigabatrin, gabapentin and oxcarbazepine [30].

Gene context of CI 945


Analytical, diagnostic and therapeutic context of CI 945


  1. Treatment of ciguatera poisoning with gabapentin. Perez, C.M., Vasquez, P.A., Perret, C.F. N. Engl. J. Med. (2001) [Pubmed]
  2. Gabapentin for postherpetic neuralgia. Colman, E., Stadel, B.V. JAMA (1999) [Pubmed]
  3. Gabapentin for painful diabetic neuropathy. Margolis, K. JAMA (1999) [Pubmed]
  4. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. Backonja, M., Beydoun, A., Edwards, K.R., Schwartz, S.L., Fonseca, V., Hes, M., LaMoreaux, L., Garofalo, E. JAMA (1998) [Pubmed]
  5. Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. Rowbotham, M., Harden, N., Stacey, B., Bernstein, P., Magnus-Miller, L. JAMA (1998) [Pubmed]
  6. Gabapentin in the treatment of bipolar disorder. Schaffer, C.B., Schaffer, L.C. The American journal of psychiatry. (1997) [Pubmed]
  7. Gabapentin as a potential treatment for anxiety disorders. Pollack, M.H., Matthews, J., Scott, E.L. The American journal of psychiatry. (1998) [Pubmed]
  8. Gabapentin for behavioral dyscontrol with mental retardation. Bozikas, V., Bascialla, F., Yulis, P., Savvidou, I., Karavatos, A. The American journal of psychiatry. (2001) [Pubmed]
  9. Treatment of idiopathic restless legs syndrome (RLS) with gabapentin. Happe, S., Klösch, G., Saletu, B., Zeitlhofer, J. Neurology (2001) [Pubmed]
  10. Clinical predictors of response to lamotrigine and gabapentin monotherapy in refractory affective disorders. Obrocea, G.V., Dunn, R.M., Frye, M.A., Ketter, T.A., Luckenbaugh, D.A., Leverich, G.S., Speer, A.M., Osuch, E.A., Jajodia, K., Post, R.M. Biol. Psychiatry (2002) [Pubmed]
  11. An astrocytic basis of epilepsy. Tian, G.F., Azmi, H., Takano, T., Xu, Q., Peng, W., Lin, J., Oberheim, N., Lou, N., Wang, X., Zielke, H.R., Kang, J., Nedergaard, M. Nat. Med. (2005) [Pubmed]
  12. The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions. Rogawski, M.A., Löscher, W. Nat. Med. (2004) [Pubmed]
  13. Effect of gabapentin on nausea induced by chemotherapy in patients with breast cancer. Guttuso, T., Roscoe, J., Griggs, J. Lancet (2003) [Pubmed]
  14. Benefit of vitamin E, riluzole, and gabapentin in a transgenic model of familial amyotrophic lateral sclerosis. Gurney, M.E., Cutting, F.B., Zhai, P., Doble, A., Taylor, C.P., Andrus, P.K., Hall, E.D. Ann. Neurol. (1996) [Pubmed]
  15. Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain. Morello, C.M., Leckband, S.G., Stoner, C.P., Moorhouse, D.F., Sahagian, G.A. Arch. Intern. Med. (1999) [Pubmed]
  16. Effects of new anticonvulsant medications on porphyrin synthesis in cultured liver cells: potential implications for patients with acute porphyria. Hahn, M., Gildemeister, O.S., Krauss, G.L., Pepe, J.A., Lambrecht, R.W., Donohue, S., Bonkovsky, H.L. Neurology (1997) [Pubmed]
  17. Importance of sleep restoration in co-morbid disease: effect of anticonvulsants. Ehrenberg, B. Neurology (2000) [Pubmed]
  18. Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin. Goto, M., Miyahara, I., Hirotsu, K., Conway, M., Yennawar, N., Islam, M.M., Hutson, S.M. J. Biol. Chem. (2005) [Pubmed]
  19. Seizures and epilepsy in the elderly. Thomas, R.J. Arch. Intern. Med. (1997) [Pubmed]
  20. Clinical pharmacokinetics of gabapentin. McLean, M.J. Neurology (1994) [Pubmed]
  21. The anticonvulsant gabapentin (neurontin) does not act through gamma-aminobutyric acid-B receptors. Jensen, A.A., Mosbacher, J., Elg, S., Lingenhoehl, K., Lohmann, T., Johansen, T.N., Abrahamsen, B., Mattsson, J.P., Lehmann, A., Bettler, B., Bräuner-Osborne, H. Mol. Pharmacol. (2002) [Pubmed]
  22. Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis. Miller, R.G., Moore, D.H., Gelinas, D.F., Dronsky, V., Mendoza, M., Barohn, R.J., Bryan, W., Ravits, J., Yuen, E., Neville, H., Ringel, S., Bromberg, M., Petajan, J., Amato, A.A., Jackson, C., Johnson, W., Mandler, R., Bosch, P., Smith, B., Graves, M., Ross, M., Sorenson, E.J., Kelkar, P., Parry, G., Olney, R. Neurology (2001) [Pubmed]
  23. Gamma-aminobutyric acid type B receptors with specific heterodimer composition and postsynaptic actions in hippocampal neurons are targets of anticonvulsant gabapentin action. Ng, G.Y., Bertrand, S., Sullivan, R., Ethier, N., Wang, J., Yergey, J., Belley, M., Trimble, L., Bateman, K., Alder, L., Smith, A., McKernan, R., Metters, K., O'Neill, G.P., Lacaille, J.C., Hébert, T.E. Mol. Pharmacol. (2001) [Pubmed]
  24. A case of spinal cord injury-related pain with baseline rCBF brain SPECT imaging and beneficial response to gabapentin. Ness, T.J., San Pedro, E.C., Richards, J.S., Kezar, L., Liu, H.G., Mountz, J.M. Pain (1998) [Pubmed]
  25. Attenuation of formalin-induced nociceptive behaviors following local peripheral injection of gabapentin. Carlton, S.M., Zhou, S. Pain (1998) [Pubmed]
  26. The effect of gabapentin on brain gamma-aminobutyric acid in patients with epilepsy. Petroff, O.A., Rothman, D.L., Behar, K.L., Lamoureux, D., Mattson, R.H. Ann. Neurol. (1996) [Pubmed]
  27. CLINICAL REVIEW: Use of antiepileptic drugs in the treatment of chronic painful diabetic neuropathy. Vinik, A. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  28. Pharmacologic treatment of pain in polyneuropathy. Sindrup, S.H., Jensen, T.S. Neurology (2000) [Pubmed]
  29. A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. Frye, M.A., Ketter, T.A., Kimbrell, T.A., Dunn, R.T., Speer, A.M., Osuch, E.A., Luckenbaugh, D.A., Cora-Ocatelli, G., Leverich, G.S., Post, R.M. Journal of clinical psychopharmacology. (2000) [Pubmed]
  30. Clinical pharmacokinetics of newer antiepileptic drugs. Lamotrigine, vigabatrin, gabapentin and oxcarbazepine. Elwes, R.D., Binnie, C.D. Clinical pharmacokinetics. (1996) [Pubmed]
  31. A nitric oxide (NO)-releasing derivative of gabapentin, NCX 8001, alleviates neuropathic pain-like behavior after spinal cord and peripheral nerve injury. Wu, W.P., Hao, J.X., Ongini, E., Impagnatiello, F., Presotto, C., Wiesenfeld-Hallin, Z., Xu, X.J. Br. J. Pharmacol. (2004) [Pubmed]
  32. Gabapentin actions on N-methyl-D-aspartate receptor channels are protein kinase C-dependent. Gu, Y., Huang, L.Y. Pain (2001) [Pubmed]
  33. Gabapentin potentiates the antiseizure activity of certain anticonvulsants in DBA/2 mice. De Sarro, G., Spagnolo, C., Gareri, P., Gallelli, L., De Sarro, A. Eur. J. Pharmacol. (1998) [Pubmed]
  34. Gabapentin in the treatment of adolescent mania: a case report. Soutullo, C.A., Casuto, L.S., Keck, P.E. Journal of child and adolescent psychopharmacology. (1998) [Pubmed]
  35. Retinal ganglion cell survival is enhanced by gabapentin-lactam in vitro: evidence for involvement of mitochondrial KATP channels. Pielen, A., Kirsch, M., Hofmann, H.D., Feuerstein, T.J., Lagrèze, W.A. Graefes Arch. Clin. Exp. Ophthalmol. (2004) [Pubmed]
  36. Gabapentin for neuropathic cancer pain: a randomized controlled trial from the Gabapentin Cancer Pain Study Group. Caraceni, A., Zecca, E., Bonezzi, C., Arcuri, E., Yaya Tur, R., Maltoni, M., Visentin, M., Gorni, G., Martini, C., Tirelli, W., Barbieri, M., De Conno, F. J. Clin. Oncol. (2004) [Pubmed]
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