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Identification
Name Gabapentin
Accession Number DB00996 (APRD00015)
Type small molecule
Groups approved
Description

Gabapentin (brand name Neurontin) is a medication originally developed for the treatment of epilepsy. Presently, gabapentin is widely used to relieve pain, especially neuropathic pain. Gabapentin is well tolerated in most patients, has a relatively mild side-effect profile, and passes through the body unmetabolized.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • gabapentin
  • Gabapentin GR
  • Gabapentine [INN-French]
  • Gabapentino [INN-Spanish]
  • Gabapentino [Spanish]
  • Gabapentinum [INN-Latin]
  • Gabapetin
Brand names
  • Aclonium
  • Neurontin
  • Novo-Gabapentin
Brand name mixtures Not Available
Categories
  • Anti-anxiety Agents
  • Anticonvulsants
  • Antiparkinson Agents
  • Analgesics
  • Calcium Channel Blockers
  • Antimanic Agents
  • Excitatory Amino Acid Antagonists
CAS number 60142-96-3
Weight Average: 171.2368
Monoisotopic: 171.125928793
Chemical Formula C9H17NO2
InChI Key InChIKey=UGJMXCAKCUNAIE-UHFFFAOYSA-N
InChI
InChI=1S/C9H17NO2/c10-7-9(6-8(11)12)4-2-1-3-5-9/h1-7,10H2,(H,11,12)
Plain Text
IUPAC Name
2-[1-(aminomethyl)cyclohexyl]acetic acid
SMILES
NCC1(CC(O)=O)CCCCC1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Amino Acids
  • Carboxylic Acids and Derivatives
Substructures
  • Amino Acids
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Carboxylic Acids and Derivatives
Pharmacology
Indication 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.
Pharmacodynamics Gabapentin, an analog of GABA, is used as an anticonvulsant to treat partial seizures, amyotrophic lateral sclerosis (ALS), and painful neuropathies. Potential uses include monotherapy of refractory partial seizure disorders, and treatment of spasticity in multiple sclerosis, tremor. mood disorders, and attenuation of disruptive behaviors in dementia. Gabapentin has high lipid solubility, is not metabolized by the liver, has no protein binding, and doesn't possess the usual drug interactions.
Mechanism of action 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.
Absorption 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).
Volume of distribution
  • 58±6 L
Protein binding Less than 3% of gabapentin circulates bound to plasma protein.
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
Clearance
  • 190 mL/min
Toxicity Symptoms of overdose include ataxia, labored breathing, ptosis, sedation, hypoactivity, and excitation.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Actavis elizabeth llc
  • Amneal pharmaceuticals ny llc
  • Apotex inc etobicoke site
  • Aurobindo pharma usa inc
  • Hikma pharmaceuticals
  • Invagen pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mutual pharmaceutical co inc
  • Ranbaxy laboratories ltd
  • Sandoz inc
  • Sun pharmaceutical industries ltd
  • Teva pharmaceuticals usa
  • Watson laboratories inc
  • Pfizer pharmaceuticals ltd
  • Parke davis div warner lambert co
  • Glenmark generics ltd
  • Matrix laboratories ltd
  • Teva pharmaceuticals usa inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Tablet Oral
Prices
Unit description Cost Unit
Gabapentin powder 30.0 USD g
Neurontin 800 mg tablet 4.73 USD tablet
Neurontin 600 mg tablet 3.94 USD tablet
Gabapentin 800 mg tablet 3.09 USD tablet
Gabapentin 600 mg tablet 2.58 USD tablet
Neurontin 400 mg Capsule 1.97 USD capsule
Neurontin 300 mg Capsule 1.67 USD capsule
Gabapentin 400 mg tablet 1.59 USD tablet
Gabapentin 300 mg tablet 1.32 USD tablet
Gabapentin 400 mg Capsule 1.21 USD capsule
Gabapentin 300 mg Capsule 1.02 USD capsule
Apo-Gabapentin 400 mg Capsule 0.76 USD capsule
Co Gabapentin 400 mg Capsule 0.76 USD capsule
Mylan-Gabapentin 400 mg Capsule 0.76 USD capsule
Novo-Gabapentin 400 mg Capsule 0.76 USD capsule
Phl-Gabapentin 400 mg Capsule 0.76 USD capsule
Pms-Gabapentin 400 mg Capsule 0.76 USD capsule
Ran-Gabapentin 400 mg Capsule 0.76 USD capsule
Ratio-Gabapentin 400 mg Capsule 0.76 USD capsule
Neurontin 100 mg Capsule 0.65 USD capsule
Apo-Gabapentin 300 mg Capsule 0.64 USD capsule
Co Gabapentin 300 mg Capsule 0.64 USD capsule
Mylan-Gabapentin 300 mg Capsule 0.64 USD capsule
Novo-Gabapentin 300 mg Capsule 0.64 USD capsule
Phl-Gabapentin 300 mg Capsule 0.64 USD capsule
Pms-Gabapentin 300 mg Capsule 0.64 USD capsule
Ran-Gabapentin 300 mg Capsule 0.64 USD capsule
Ratio-Gabapentin 300 mg Capsule 0.64 USD capsule
Gabapentin 100 mg tablet 0.53 USD tablet
Gabapentin 100 mg Capsule 0.41 USD capsule
Neurontin 250 mg/5ml Solution 0.32 USD ml
Apo-Gabapentin 100 mg Capsule 0.26 USD capsule
Co Gabapentin 100 mg Capsule 0.26 USD capsule
Mylan-Gabapentin 100 mg Capsule 0.26 USD capsule
Novo-Gabapentin 100 mg Capsule 0.26 USD capsule
Phl-Gabapentin 100 mg Capsule 0.26 USD capsule
Pms-Gabapentin 100 mg Capsule 0.26 USD capsule
Ran-Gabapentin 100 mg Capsule 0.26 USD capsule
Ratio-Gabapentin 100 mg Capsule 0.26 USD capsule
Patents
Country Patent Number Approved Expires
United States 7256216 2002-11-28 2022-11-28
United States 6054482 1997-04-25 2017-04-25
Canada 2327285 2005-06-14 2019-05-10
Canada 2215923 2001-10-09 2016-04-26
Properties
State solid
Melting point 162-166 oC
Experimental Properties
Property Value Source
water solubility 4490 mg/L PhysProp
logP 1.4 PhysProp
Predicted Properties
Property Value Source
water solubility 4.34e+00 g/l ALOGPS
logP -1.88 ALOGPS
logP -1.51 ChemAxon Molconvert
logS -1.60 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 63.32 ChemAxon Molconvert
rotatable bond count 3 ChemAxon Molconvert
refractivity 46.33 ChemAxon Molconvert
polarizability 18.92 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. 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. Pubmed
  2. Backonja MM, Serra J: Pharmacologic management part 1: better-studied neuropathic pain diseases. Pain Med. 2004 Mar;5 Suppl 1:S28-47. Pubmed
  3. Choudhuri I, Sarvananthan N, Gottlob I: Survey of management of acquired nystagmus in the United Kingdom. Eye. 2007 Sep;21(9):1194-7. Epub 2006 May 26. Pubmed
  4. 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. Pubmed
External Links
Resource Link
KEGG Drug D00332 Link_out
PubChem Compound 3446 Link_out
PubChem Substance 46506529 Link_out
ChemSpider 3328 Link_out
Therapeutic Targets Database DNC000670 Link_out
PharmGKB PA449720 Link_out
HET GBN Link_out
Drug Product Database 2260905 Link_out
RxList http://www.rxlist.com/cgi/generic/gabapent.htm Link_out
Drugs.com http://www.drugs.com/gabapentin.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/neu1289.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Gabapentin Link_out
ATC Codes
  • N03AX12
AHFS Codes
  • 28:12.92
PDB Entries Not Available
FDA label show (1.5 MB)
MSDS show (73.3 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.
Targets

1. Voltage-dependent calcium channel subunit alpha-2/delta-1

Pharmacological action: yes
Actions: inhibitor

Calcium channel protein which plays an important role in excitation-contraction coupling

Organism class: human
UniProt ID: P54289 Link_out
Gene: CACNA2D1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Maneuf YP, Luo ZD, Lee K: alpha2delta and the mechanism of action of gabapentin in the treatment of pain. Semin Cell Dev Biol. 2006 Oct;17(5):565-70. Epub 2006 Sep 24. Pubmed
  2. Hota D, Bansal V, Pattanaik S: Evaluation of ketamine, nimodipine, gabapentin and imipramine in partial sciatic nerve transection model of neuropathic pain in rat: an experimental study. Methods Find Exp Clin Pharmacol. 2007 Sep;29(7):443-6. Pubmed
  3. Gazulla J, Tintore MA: The P/Q-type voltage-dependent calcium channel as pharmacological target in spinocerebellar ataxia type 6: gabapentin and pregabalin may be of therapeutic benefit. Med Hypotheses. 2007;68(1):131-6. Epub 2006 Aug 8. Pubmed
  4. Hendrich J, Van Minh AT, Heblich F, Nieto-Rostro M, Watschinger K, Striessnig J, Wratten J, Davies A, Dolphin AC: Pharmacological disruption of calcium channel trafficking by the alpha2delta ligand gabapentin. Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3628-33. Epub 2008 Feb 25. Pubmed
  5. Hoffmann U, Dilekoz E, Kudo C, Ayata C: Gabapentin suppresses cortical spreading depression susceptibility. J Cereb Blood Flow Metab. 2010 Sep;30(9):1588-92. Epub 2010 Jun 30. Pubmed

2. Voltage-dependent calcium channel subunit alpha-2/delta-2

Pharmacological action: yes
Actions: inhibitor
Organism class: human
UniProt ID: Q9NY47 Link_out
Gene: CACNA2D2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hota D, Bansal V, Pattanaik S: Evaluation of ketamine, nimodipine, gabapentin and imipramine in partial sciatic nerve transection model of neuropathic pain in rat: an experimental study. Methods Find Exp Clin Pharmacol. 2007 Sep;29(7):443-6. Pubmed
  2. Gazulla J, Tintore MA: The P/Q-type voltage-dependent calcium channel as pharmacological target in spinocerebellar ataxia type 6: gabapentin and pregabalin may be of therapeutic benefit. Med Hypotheses. 2007;68(1):131-6. Epub 2006 Aug 8. Pubmed
  3. Hendrich J, Van Minh AT, Heblich F, Nieto-Rostro M, Watschinger K, Striessnig J, Wratten J, Davies A, Dolphin AC: Pharmacological disruption of calcium channel trafficking by the alpha2delta ligand gabapentin. Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3628-33. Epub 2008 Feb 25. Pubmed
  4. Hoffmann U, Dilekoz E, Kudo C, Ayata C: Gabapentin suppresses cortical spreading depression susceptibility. J Cereb Blood Flow Metab. 2010 Sep;30(9):1588-92. Epub 2010 Jun 30. Pubmed

3. Voltage-dependent N-type calcium channel subunit alpha-1B

Pharmacological action: yes
Actions: inhibitor

Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the "high-voltage activated" (HVA) group and are blocked by omega-conotoxin-GVIA (omega-CTx-GVIA) and by omega-agatoxin- IIIA (omega-Aga-IIIA). They are however insensitive to dihydropyridines (DHP), and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons

Organism class: human
UniProt ID: Q00975 Link_out
Gene: CACNA1B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cheng JK, Chen CC, Yang JR, Chiou LC: The antiallodynic action target of intrathecal gabapentin: Ca2+ channels, KATP channels or N-methyl-d-aspartic acid receptors? Anesth Analg. 2006 Jan;102(1):182-7. Pubmed
  2. Hendrich J, Van Minh AT, Heblich F, Nieto-Rostro M, Watschinger K, Striessnig J, Wratten J, Davies A, Dolphin AC: Pharmacological disruption of calcium channel trafficking by the alpha2delta ligand gabapentin. Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3628-33. Epub 2008 Feb 25. Pubmed
  3. Hoffmann U, Dilekoz E, Kudo C, Ayata C: Gabapentin suppresses cortical spreading depression susceptibility. J Cereb Blood Flow Metab. 2010 Sep;30(9):1588-92. Epub 2010 Jun 30. Pubmed

4. Adenosine A1 receptor

Pharmacological action: unknown
Actions: agonist

Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P30542 Link_out
Gene: ADORA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. De Vry J, Kuhl E, Franken-Kunkel P, Eckel G: Pharmacological characterization of the chronic constriction injury model of neuropathic pain. Eur J Pharmacol. 2004 May 3;491(2-3):137-48. Pubmed
  2. Zuchora B, Wielosz M, Urbanska EM: Adenosine A1 receptors and the anticonvulsant potential of drugs effective in the model of 3-nitropropionic acid-induced seizures in mice. Eur Neuropsychopharmacol. 2005 Jan;15(1):85-93. Pubmed
  3. Kralic JE, Criswell HE, Osterman JL, O’Buckley TK, Wilkie ME, Matthews DB, Hamre K, Breese GR, Homanics GE, Morrow AL: Genetic essential tremor in gamma-aminobutyric acidA receptor alpha1 subunit knockout mice. J Clin Invest. 2005 Mar;115(3):774-9. Pubmed
Enzymes

1. Branched-chain-amino-acid aminotransferase, cytosolic

Actions: inhibitor

Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine

UniProt ID: P54687 Link_out
Gene: BCAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Goto M, Miyahara I, Hirotsu K, Conway M, Yennawar N, Islam MM, Hutson SM: Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin. J Biol Chem. 2005 Nov 4;280(44):37246-56. Epub 2005 Sep 1. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 24, 2010 16:26

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.