Record Information |
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Version | 2.0 |
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Creation Date | 2009-07-21 20:28:07 UTC |
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Update Date | 2014-12-24 20:25:54 UTC |
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Accession Number | T3D2952 |
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Identification |
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Common Name | Gabapentin |
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Class | Small Molecule |
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Description | Gabapentin was originally developed as a chemical analogue of gamma-aminobutyric acid (GABA) to reduce the spinal reflex for the treatment of spasticity and was found to have anticonvulsant activity in various seizure models. In addition, it also displays antinociceptive activity in various animal pain models. Clinically, gabapentin is indicated as an add-on medication for the treatment of partial seizures, and neuropathic pain. It was also claimed to be beneficial in several other clinical disorders such as anxiety, bipolar disorder, and hot flashes. The possible mechanisms or targets involved in the multiple therapeutic actions of gabapentin have been actively studied. Since gabapentin was developed, several hypotheses had been proposed for its action mechanisms. They include selectively activating the heterodimeric GABA(B) receptors consisting of GABA(B1a) and GABA(B2) subunits, selectively enhancing the NMDA current at GABAergic interneurons, or blocking AMPA-receptor-mediated transmission in the spinal cord, binding to the L-alpha-amino acid transporter, activating ATP-sensitive K(+) channels, activating hyperpolarization-activated cation channels, and modulating Ca(2+) current by selectively binding to the specific binding site of [(3)H]gabapentin, the alpha(2)delta subunit of voltage-dependent Ca(2+) channels. Different mechanisms might be involved in different therapeutic actions of gabapentin. In this review, we summarized the recent progress in the findings proposed for the antinociceptive action mechanisms of gabapentin and suggest that the alpha(2)delta subunit of spinal N-type Ca(2+) channels is very likely the analgesic action target of gabapentin. (5). |
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Compound Type | - Amine
- Analgesic
- Anti-Anxiety Agent
- Anticonvulsant
- Antimanic Agent
- Antiparkinson Agent
- Calcium Channel Blocker
- Drug
- Excitatory Amino Acid Antagonist
- Food Toxin
- Metabolite
- Organic Compound
- Synthetic Compound
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Chemical Structure | |
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Synonyms | Synonym | 1-(Aminomethyl)cyclohexaneacetic acid | Aclonium | Gabapentin GR | Gabapentina | Gabapentine | Gabapentino | Gabapentinum | Gabapetin | Gralise | Neurontin | Novo-Gabapentin | Novo-Gabapentine |
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Chemical Formula | C9H17NO2 |
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Average Molecular Mass | 171.237 g/mol |
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Monoisotopic Mass | 171.126 g/mol |
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CAS Registry Number | 60142-96-3 |
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IUPAC Name | 2-[1-(aminomethyl)cyclohexyl]acetic acid |
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Traditional Name | gabapentin |
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SMILES | NCC1(CC(O)=O)CCCCC1 |
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InChI Identifier | InChI=1S/C9H17NO2/c10-7-9(6-8(11)12)4-2-1-3-5-9/h1-7,10H2,(H,11,12) |
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InChI Key | InChIKey=UGJMXCAKCUNAIE-UHFFFAOYSA-N |
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Chemical Taxonomy |
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Description | belongs to the class of organic compounds known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom. |
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Kingdom | Organic compounds |
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Super Class | Organic acids and derivatives |
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Class | Carboxylic acids and derivatives |
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Sub Class | Amino acids, peptides, and analogues |
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Direct Parent | Gamma amino acids and derivatives |
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Alternative Parents | |
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Substituents | - Gamma amino acid or derivatives
- Amino fatty acid
- Fatty acyl
- Amino acid
- Carboxylic acid
- Monocarboxylic acid or derivatives
- Organopnictogen compound
- Primary amine
- Organooxygen compound
- Organonitrogen compound
- Amine
- Primary aliphatic amine
- Organic oxygen compound
- Carbonyl group
- Organic nitrogen compound
- Hydrocarbon derivative
- Organic oxide
- Aliphatic homomonocyclic compound
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Molecular Framework | Aliphatic homomonocyclic compounds |
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External Descriptors | |
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Biological Properties |
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Status | Detected and Not Quantified |
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Origin | Exogenous |
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Cellular Locations | |
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Biofluid Locations | Not Available |
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Tissue Locations | |
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Pathways | Not Available |
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Applications | |
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Biological Roles | |
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Chemical Roles | Not Available |
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Physical Properties |
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State | Solid |
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Appearance | White powder. |
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Experimental Properties | Property | Value |
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Melting Point | 162-166°C | Boiling Point | Not Available | Solubility | 4490 mg/L | LogP | -1.1 |
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Predicted Properties | |
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Spectra |
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Spectra | Spectrum Type | Description | Splash Key | Deposition Date | View |
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Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | splash10-001i-9300000000-1b1c66a2b9ea4333921d | 2017-09-01 | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive | splash10-00ai-9520000000-9cbc5f48f228d49f903c | 2017-10-06 | View Spectrum | Predicted GC-MS | Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive | Not Available | 2021-10-12 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QTOF , negative | splash10-00di-0900000000-bccc9bd5f1637db7b6c7 | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QTOF , negative | splash10-00di-0900000000-67139ca9559173bf9859 | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QTOF , negative | splash10-0006-9000000000-bfe6527f738e4c67eb2b | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QTOF , positive | splash10-00di-0900000000-bb175ef297a289e1936b | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QTOF , positive | splash10-0udr-0900000000-258d4493623d0ab7b415 | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-QTOF , positive | splash10-0f79-0900000000-bc24764f394c6fee34fd | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-ITFT , positive | splash10-0udi-0900000000-006ecd4a58af763b087f | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-ITFT , positive | splash10-00di-0900000000-012c52738f11970adb8d | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-ITFT , positive | splash10-00di-0900000000-8f0d390195aa406adb5d | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-ITFT , positive | splash10-0uk9-0900000000-72f8d5cb88eda76dab56 | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-ITFT , positive | splash10-0udi-3900000000-b634b4e7144ec6ffdc83 | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-ITFT , positive | splash10-0ktn-9800000000-20c4131179b228ab3440 | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-ITFT , positive | splash10-00ke-9300000000-dd9d44ed4f16961ed075 | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-ITFT , positive | splash10-00di-0900000000-f9a7deaa778e9d893ee8 | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-ITFT , positive | splash10-00di-0900000000-4f85e6ac9fd91a3e3b81 | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-ITFT , positive | splash10-0uk9-0900000000-d3a4c5658e343cf3cf8d | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-ITFT , positive | splash10-0udi-3900000000-712133d5b9eae1b27ffb | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-ITFT , positive | splash10-0ktn-9800000000-c652847259e0851b428e | 2017-09-14 | View Spectrum | LC-MS/MS | LC-MS/MS Spectrum - LC-ESI-ITFT , positive | splash10-00ke-9200000000-77e258cf26b045a7e46e | 2017-09-14 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-0kmi-0900000000-bd606c1e84a1821141d5 | 2016-08-03 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-0a6r-1900000000-7e1f93e356d99c221d79 | 2016-08-03 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-0a4l-9400000000-e7cad8847543c27e9be7 | 2016-08-03 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-00fr-0900000000-46b0ef53eef895d16407 | 2016-08-03 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-00fr-1900000000-49d03843c6afc2b38719 | 2016-08-03 | View Spectrum | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-0a4i-7900000000-21b2e487e51f606cc2ad | 2016-08-03 | View Spectrum | 1D NMR | 1H NMR Spectrum (1D, 600 MHz, H2O, experimental) | Not Available | 2012-12-05 | View Spectrum | 1D NMR | 1H NMR Spectrum (1D, 100 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 13C NMR Spectrum (1D, 100 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 1H NMR Spectrum (1D, 1000 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 13C NMR Spectrum (1D, 1000 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 1H NMR Spectrum (1D, 200 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 13C NMR Spectrum (1D, 200 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 1H NMR Spectrum (1D, 300 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 13C NMR Spectrum (1D, 300 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 1H NMR Spectrum (1D, 400 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 13C NMR Spectrum (1D, 400 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 1H NMR Spectrum (1D, 500 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 13C NMR Spectrum (1D, 500 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 1H NMR Spectrum (1D, 600 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 13C NMR Spectrum (1D, 600 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 1H NMR Spectrum (1D, 700 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 13C NMR Spectrum (1D, 700 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 1H NMR Spectrum (1D, 800 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 13C NMR Spectrum (1D, 800 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 1H NMR Spectrum (1D, 900 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 1D NMR | 13C NMR Spectrum (1D, 900 MHz, D2O, predicted) | Not Available | 2021-09-24 | View Spectrum | 2D NMR | [1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental) | Not Available | 2012-12-05 | View Spectrum |
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Toxicity Profile |
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Route of Exposure | Oral. Rapid. Absorbed in part by the L-amino acid transport system, which is a carrier-mediated, saturable transport system; as the dose increases, bioavailability decreases. Bioavailability ranges from approximately 60% for a 900 mg dose per day to approximately 27% for a 4800 milligram dose per day. Food has a slight effect on the rate and extent of absorption of gabapentin (14% increase in AUC). |
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Mechanism of Toxicity | Gabapentin interacts with cortical neurons at auxillary subunits of voltage-sensitive calcium channels. Gabapentin increases the synaptic concentration of GABA, enhances GABA responses at non-synaptic sites in neuronal tissues, and reduces the release of mono-amine neurotransmitters. One of the mechanisms implicated in this effect of gabapentin is the reduction of the axon excitability measured as an amplitude change of the presynaptic fibre volley (FV) in the CA1 area of the hippocampus. This is mediated through its binding to presynaptic NMDA receptors. Other studies have shown that the antihyperalgesic and antiallodynic effects of gabapentin are mediated by the descending noradrenergic system, resulting in the activation of spinal alpha2-adrenergic receptors. Gabapentin has also been shown to bind and activate the adenosine A1 receptor. |
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Metabolism | All pharmacological actions following gabapentin administration are due to the activity of the parent compound; gabapentin is not appreciably metabolized in humans.
Route of Elimination: Gabapentin is eliminated from the systemic circulation by renal excretion as unchanged drug.
Gabapentin is not appreciably metabolized in humans.
Half Life: 5-7 hours |
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Toxicity Values | LD50: >8000 mg/kg (oral,rat) [MSDS]
LD50: 8053 mg/kg (oral, mouse) [MSDS] |
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Lethal Dose | Not Available |
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Carcinogenicity (IARC Classification) | No indication of carcinogenicity to humans (not listed by IARC). |
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Uses/Sources | It was originally developed for the treatment of epilepsy, and currently, gabapentin is widely used to relieve pain, especially neuropathic pain. [wikipedia]. For the management of postherpetic neuralgia in adults and as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in patients over 12 years of age with epilepsy. |
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Minimum Risk Level | Not Available |
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Health Effects | May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease. |
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Symptoms | Symptoms of overdose include ataxia, labored breathing, ptosis, sedation, hypoactivity, and excitation. |
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Treatment | Gabapentin can be removed by hemodialysis. (14) |
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Normal Concentrations |
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| Not Available |
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Abnormal Concentrations |
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| Not Available |
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External Links |
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DrugBank ID | DB00996 |
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HMDB ID | HMDB05015 |
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PubChem Compound ID | 3446 |
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ChEMBL ID | CHEMBL940 |
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ChemSpider ID | 3328 |
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KEGG ID | Not Available |
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UniProt ID | Not Available |
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OMIM ID | |
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ChEBI ID | 42797 |
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BioCyc ID | Not Available |
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CTD ID | Not Available |
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Stitch ID | Gabapentin |
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PDB ID | GBN |
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ACToR ID | Not Available |
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Wikipedia Link | Gabapentin |
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References |
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Synthesis Reference | Donald E. Butler, Barbara J. Greenman, “Gabapentin mohohydrate and a process for producing the same.” U.S. Patent US4960931, issued May, 1978. |
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MSDS | Link |
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General References | - Mathew NT, Rapoport A, Saper J, Magnus L, Klapper J, Ramadan N, Stacey B, Tepper S: Efficacy of gabapentin in migraine prophylaxis. Headache. 2001 Feb;41(2):119-28. [11251695 ]
- Backonja MM, Serra J: Pharmacologic management part 1: better-studied neuropathic pain diseases. Pain Med. 2004 Mar;5 Suppl 1:S28-47. [14996228 ]
- Choudhuri I, Sarvananthan N, Gottlob I: Survey of management of acquired nystagmus in the United Kingdom. Eye (Lond). 2007 Sep;21(9):1194-7. Epub 2006 May 26. [16732211 ]
- Pande AC, Crockatt JG, Janney CA, Werth JL, Tsaroucha G: Gabapentin in bipolar disorder: a placebo-controlled trial of adjunctive therapy. Gabapentin Bipolar Disorder Study Group. Bipolar Disord. 2000 Sep;2(3 Pt 2):249-55. [11249802 ]
- Cheng JK, Chiou LC: Mechanisms of the antinociceptive action of gabapentin. J Pharmacol Sci. 2006;100(5):471-86. Epub 2006 Feb 11. [16474201 ]
- Su TZ, Feng MR, Weber ML: Mediation of highly concentrative uptake of pregabalin by L-type amino acid transport in Chinese hamster ovary and Caco-2 cells. J Pharmacol Exp Ther. 2005 Jun;313(3):1406-15. Epub 2005 Mar 15. [15769862 ]
- Nemeroff CB: The role of GABA in the pathophysiology and treatment of anxiety disorders. Psychopharmacol Bull. 2003;37(4):133-46. [15131523 ]
- Di Trapani G, Mei D, Marra C, Mazza S, Capuano A: Gabapentin in the prophylaxis of migraine: a double-blind randomized placebo-controlled study. Clin Ter. 2000 May-Jun;151(3):145-8. [10958046 ]
- Bisaga A, Aharonovich E, Garawi F, Levin FR, Rubin E, Raby WN, Nunes EV: A randomized placebo-controlled trial of gabapentin for cocaine dependence. Drug Alcohol Depend. 2006 Feb 28;81(3):267-74. Epub 2005 Oct 5. [16169160 ]
- Petroff OA, Rothman DL, Behar KL, Lamoureux D, Mattson RH: The effect of gabapentin on brain gamma-aminobutyric acid in patients with epilepsy. Ann Neurol. 1996 Jan;39(1):95-9. [8572673 ]
- Taylor CP, Gee NS, Su TZ, Kocsis JD, Welty DF, Brown JP, Dooley DJ, Boden P, Singh L: A summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Res. 1998 Feb;29(3):233-49. [9551785 ]
- Czapinski P, Blaszczyk B, Czuczwar SJ: Mechanisms of action of antiepileptic drugs. Curr Top Med Chem. 2005;5(1):3-14. [15638774 ]
- Drugs.com [Link]
- RxList: The Internet Drug Index (2009). [Link]
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Gene Regulation |
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Up-Regulated Genes | Not Available |
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Down-Regulated Genes | Not Available |
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