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Record Information
Version3.6
Creation Date2006-10-17 08:37:49 UTC
Update Date2014-09-23 05:28:22 UTC
HMDB IDHMDB05015
Secondary Accession NumbersNone
Metabolite Identification
Common NameGabapentin
DescriptionGabapentin 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. (PMID: 16474201 ).
Structure
Thumb
Synonyms
  1. Neurontin
  2. 1-(Aminomethyl)cyclohexaneacetic acid
  3. Aclonium
  4. Gabapentin
  5. Gabapentine
  6. Gabapentino
  7. Gabapentinum
  8. Gabapetin
  9. Novo-Gabapentine
Chemical FormulaC9H17NO2
Average Molecular Weight171.2368
Monoisotopic Molecular Weight171.125928793
IUPAC Name2-[1-(aminomethyl)cyclohexyl]acetic acid
Traditional Namegabapentin
CAS Registry Number60142-96-3
SMILES
NCC1(CC(O)=O)CCCCC1
InChI Identifier
InChI=1S/C9H17NO2/c10-7-9(6-8(11)12)4-2-1-3-5-9/h1-7,10H2,(H,11,12)
InChI KeyUGJMXCAKCUNAIE-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAmino Acids, Peptides, and Analogues
ClassAmino Acids and Derivatives
Sub ClassGamma Amino Acids and Derivatives
Other Descriptors
  • Aliphatic Homomonocyclic Compounds
Substituents
  • Carboxylic Acid
  • Cyclohexane
  • Primary Aliphatic Amine (Alkylamine)
Direct ParentGamma Amino Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Drug
Biofunction
  • Protein synthesis, amino acid biosynthesis
ApplicationNot Available
Cellular locationsNot Available
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point165 - 167 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot 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
Polarizability18.88 Å3ChemAxon
Spectra
Spectra1D NMR2D NMR
Biological Properties
Cellular LocationsNot Available
Biofluid Locations
  • Blood
Tissue Location
  • Brain
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.31 +/- 0.012 uMAdult (>18 years old)BothNormal details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-3 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB023587
KNApSAcK IDNot Available
Chemspider ID3328
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkGabapentin
NuGOwiki LinkHMDB05015
Metagene LinkHMDB05015
METLIN ID2989
PubChem Compound3446
PDB IDGBN
ChEBI IDNot Available
References
Synthesis ReferenceSatzinger, Gerhard; Hartenstein, Johannes; Herrmann, Manfred; Heldt, Wolfgang. Cyclic amino acids. Ger. Offen. (1976), 16 pp. CODEN: GWXXBX DE 2460891 19760701 CAN 85:94679 AN 1976:494679
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Nemeroff CB: The role of GABA in the pathophysiology and treatment of anxiety disorders. Psychopharmacol Bull. 2003;37(4):133-46. Pubmed: 15131523
  2. 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. Pubmed: 10958046
  3. 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. Pubmed: 16169160
  4. 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. Pubmed: 8572673
  5. 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. Pubmed: 9551785
  6. Czapinski P, Blaszczyk B, Czuczwar SJ: Mechanisms of action of antiepileptic drugs. Curr Top Med Chem. 2005;5(1):3-14. Pubmed: 15638774
  7. Cheng JK, Chiou LC: Mechanisms of the antinociceptive action of gabapentin. J Pharmacol Sci. 2006;100(5):471-86. Epub 2006 Feb 11. Pubmed: 16474201

Enzymes

General function:
Involved in catalytic activity
Specific function:
Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine.
Gene Name:
BCAT1
Uniprot ID:
P54687
Molecular weight:
38644.77
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase
Gene Name:
ADORA1
Uniprot ID:
P30542
Molecular weight:
36511.3
General function:
Involved in metal ion binding
Specific function:
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-contraction coupling
Gene Name:
CACNA2D1
Uniprot ID:
P54289
Molecular weight:
124566.9
General function:
Involved in calcium channel activity
Specific function:
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G). Overexpression induces apoptosis
Gene Name:
CACNA2D2
Uniprot ID:
Q9NY47
Molecular weight:
129875.2
General function:
Involved in ion channel activity
Specific function:
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
Gene Name:
CACNA1B
Uniprot ID:
Q00975
Molecular weight:
262493.8