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Identification
NameGabapentin
Accession NumberDB00996  (APRD00015)
TypeSmall Molecule
GroupsApproved, Investigational
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
Synonyms
SynonymLanguageCode
1-(Aminomethyl)cyclohexaneacetic acidNot AvailableNot Available
Gabapentin GRNot AvailableNot Available
GabapentinaNot AvailableNot Available
GabapentineFrenchINN
GabapentinoSpanishNot Available
GabapentinumLatinINN
GabapetinNot AvailableNot Available
NeurontinNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AcloniumNot Available
GraliseNot Available
NeurontinNot Available
Novo-GabapentinNot Available
Brand mixturesNot Available
Categories
CAS number60142-96-3
WeightAverage: 171.2368
Monoisotopic: 171.125928793
Chemical FormulaC9H17NO2
InChI KeyUGJMXCAKCUNAIE-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)
IUPAC Name
2-[1-(aminomethyl)cyclohexyl]acetic acid
SMILES
NCC1(CC(O)=O)CCCCC1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentGamma Amino Acids and Derivatives
Alternative parentsPolyamines; Enolates; Carboxylic Acids; Monoalkylamines
Substituentscarboxylic acid; enolate; polyamine; primary amine; amine; primary aliphatic amine; organonitrogen compound
Classification descriptionThis compound belongs to the gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom.
Pharmacology
IndicationFor 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.
PharmacodynamicsGabapentin, 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 actionGabapentin 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.
AbsorptionRapid. 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 bindingLess 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 eliminationGabapentin is eliminated from the systemic circulation by renal excretion as unchanged drug. Gabapentin is not appreciably metabolized in humans.
Half life5-7 hours
Clearance
  • 190 mL/min
ToxicitySymptoms of overdose include ataxia, labored breathing, ptosis, sedation, hypoactivity, and excitation.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.941
Blood Brain Barrier + 0.9382
Caco-2 permeable - 0.7271
P-glycoprotein substrate Non-substrate 0.6557
P-glycoprotein inhibitor I Non-inhibitor 0.9789
P-glycoprotein inhibitor II Non-inhibitor 0.8866
Renal organic cation transporter Non-inhibitor 0.7982
CYP450 2C9 substrate Non-substrate 0.893
CYP450 2D6 substrate Non-substrate 0.8124
CYP450 3A4 substrate Non-substrate 0.7612
CYP450 1A2 substrate Non-inhibitor 0.9409
CYP450 2C9 substrate Non-inhibitor 0.9273
CYP450 2D6 substrate Non-inhibitor 0.9418
CYP450 2C19 substrate Non-inhibitor 0.9547
CYP450 3A4 substrate Non-inhibitor 0.8438
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9706
Ames test Non AMES toxic 0.9162
Carcinogenicity Non-carcinogens 0.8536
Biodegradation Not ready biodegradable 0.7046
Rat acute toxicity 1.6472 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9406
hERG inhibition (predictor II) Non-inhibitor 0.8659
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
FormRouteStrength
CapsuleOral
TabletOral
Prices
Unit descriptionCostUnit
Gabapentin powder30.0USDg
Neurontin 800 mg tablet4.73USDtablet
Neurontin 600 mg tablet3.94USDtablet
Gabapentin 800 mg tablet3.09USDtablet
Gabapentin 600 mg tablet2.58USDtablet
Neurontin 400 mg Capsule1.97USDcapsule
Neurontin 300 mg Capsule1.67USDcapsule
Gabapentin 400 mg tablet1.59USDtablet
Gabapentin 300 mg tablet1.32USDtablet
Gabapentin 400 mg Capsule1.21USDcapsule
Gabapentin 300 mg Capsule1.02USDcapsule
Apo-Gabapentin 400 mg Capsule0.76USDcapsule
Co Gabapentin 400 mg Capsule0.76USDcapsule
Mylan-Gabapentin 400 mg Capsule0.76USDcapsule
Novo-Gabapentin 400 mg Capsule0.76USDcapsule
Phl-Gabapentin 400 mg Capsule0.76USDcapsule
Pms-Gabapentin 400 mg Capsule0.76USDcapsule
Ran-Gabapentin 400 mg Capsule0.76USDcapsule
Ratio-Gabapentin 400 mg Capsule0.76USDcapsule
Neurontin 100 mg Capsule0.65USDcapsule
Apo-Gabapentin 300 mg Capsule0.64USDcapsule
Co Gabapentin 300 mg Capsule0.64USDcapsule
Mylan-Gabapentin 300 mg Capsule0.64USDcapsule
Novo-Gabapentin 300 mg Capsule0.64USDcapsule
Phl-Gabapentin 300 mg Capsule0.64USDcapsule
Pms-Gabapentin 300 mg Capsule0.64USDcapsule
Ran-Gabapentin 300 mg Capsule0.64USDcapsule
Ratio-Gabapentin 300 mg Capsule0.64USDcapsule
Gabapentin 100 mg tablet0.53USDtablet
Gabapentin 100 mg Capsule0.41USDcapsule
Neurontin 250 mg/5ml Solution0.32USDml
Apo-Gabapentin 100 mg Capsule0.26USDcapsule
Co Gabapentin 100 mg Capsule0.26USDcapsule
Mylan-Gabapentin 100 mg Capsule0.26USDcapsule
Novo-Gabapentin 100 mg Capsule0.26USDcapsule
Phl-Gabapentin 100 mg Capsule0.26USDcapsule
Pms-Gabapentin 100 mg Capsule0.26USDcapsule
Ran-Gabapentin 100 mg Capsule0.26USDcapsule
Ratio-Gabapentin 100 mg Capsule0.26USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States72562162002-11-282022-11-28
United States60544821997-04-252017-04-25
Canada23272852005-06-142019-05-10
Canada22159232001-10-092016-04-26
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point162-166 °CNot Available
water solubility4490 mg/LNot Available
logP-1.10SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility4.34ALOGPS
logP-1.9ALOGPS
logP-1.3ChemAxon
logS-1.6ALOGPS
pKa (Strongest Acidic)4.63ChemAxon
pKa (Strongest Basic)9.91ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area63.32 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity46.33 m3·mol-1ChemAxon
Polarizability18.92 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra1D NMR2D NMR
References
Synthesis Reference

Donald E. Butler, Barbara J. Greenman, “Gabapentin mohohydrate and a process for producing the same.” U.S. Patent US4960931, issued May, 1978.

US4960931
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
  5. 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. Pubmed
External Links
ResourceLink
KEGG DrugD00332
PubChem Compound3446
PubChem Substance46506529
ChemSpider3328
Therapeutic Targets DatabaseDNC000670
PharmGKBPA449720
HETGBN
Drug Product Database2260905
RxListhttp://www.rxlist.com/cgi/generic/gabapent.htm
Drugs.comhttp://www.drugs.com/gabapentin.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/neu1289.shtml
WikipediaGabapentin
ATC CodesN03AX12
AHFS Codes
  • 28:12.92
PDB EntriesNot Available
FDA labelshow(1.5 MB)
MSDSshow(73.3 KB)
Interactions
Drug Interactions
Drug
EthotoinIncreases the effect of hydantoin
FosphenytoinGabapentin may increase the effect of fosphenytoin.
MephenytoinIncreases the effect of hydantoin
PhenytoinGabapentin may increase the therapeutic and adverse effects of phenytoin.
TriprolidineThe CNS depressants, Triprolidine and Gabapentin, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.

Targets

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent calcium channel subunit alpha-2/delta-1 P54289 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent calcium channel subunit alpha-2/delta-2 Q9NY47 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Voltage-dependent N-type calcium channel subunit alpha-1B Q00975 Details

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 receptor A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Adenosine receptor A1 P30542 Details

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

5. NMDA receptor

Kind: protein group

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Glutamate receptor ionotropic, NMDA 1 Q05586 Details
Glutamate receptor ionotropic, NMDA 2A Q12879 Details
Glutamate receptor ionotropic, NMDA 2B Q13224 Details
Glutamate receptor ionotropic, NMDA 2C Q14957 Details
Glutamate receptor ionotropic, NMDA 2D O15399 Details
Glutamate receptor ionotropic, NMDA 3A Q8TCU5 Details
Glutamate receptor ionotropic, NMDA 3B O60391 Details

References:

  1. Shimoyama M, Shimoyama N, Hori Y: Gabapentin affects glutamatergic excitatory neurotransmission in the rat dorsal horn. Pain. 2000 Apr;85(3):405-14. Pubmed

Enzymes

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Branched-chain-amino-acid aminotransferase, cytosolic P54687 Details

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
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12