PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
gabapentin

2D structure

Overview

Generic Names: Gabapentin GR; Gabapentine [INN-French]; Gabapentino [INN-Spanish]; Gabapentino [Spanish]; Gabapentinum [INN-Latin]; Gabapetin; gabapentin
Trade Names: Aclonium; Neurontin; Novo-Gabapentin
PharmGKB Accession Id: PA449720

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. (source: Drug Bank)

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. (source: Drug Bank)

ATC Therapeutic Category

  • N03AX:Other antiepileptics

Pharmacology, Interactions, and Contraindications

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. (source: Drug Bank)

Pharmacology

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. (source: Drug Bank)

Food Interactions

Avoid alcohol.
Take without regard to meals. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

All pharmacological actions following gabapentin administration are due to the activity of the parent compound; gabapentin is not appreciably metabolized in humans. (source: Drug Bank)

Protein Binding

Less than 3% of gabapentin circulates bound to plasma protein. (source: Drug Bank)

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). (source: Drug Bank)

Toxicity

Symptoms of overdose include ataxia, labored breathing, ptosis, sedation, hypoactivity, and excitation. (source: Drug Bank)

Isomeric SMILES Code:

C1CCC(CC1)(CC(=O)O)CN (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs2032582 at chr7:86998554 in ABCB1
    This variant maybe associated with drug resistance in chinese epilepsy patients. Sample size: 464 chinese epilepsy patients (270 drug responsive, 194 drug resistant).
    Variant Name:
    ABCB1: 2677T/A>G
    Related Drugs:
    carbamazepine, clobazam, clonazepam, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, topiramate, valproic acid, vigabatrin
    Related Diseases:
    Epilepsy
    Evidence:
    PMID:19450124
  2. rs3789243 at chr7:87058822 in ABCB1
    This variant maybe associated with drug resistance in chinese epilepsy patients. Sample size: 464 chinese epilepsy patients (270 drug responsive, 194 drug resistant).
    Related Drugs:
    carbamazepine, clobazam, clonazepam, gabapentin, lamotrigine, levetiracetam, phenobarbital, phenytoin, topiramate, valproic acid, vigabatrin
    Related Diseases:
    Epilepsy
    Evidence:
    PMID:19450124

Non-Curated Annotations (Non-Curated Annotation)

  1. rs1050152 at chr5:131704219 in SLC22A4
    Higher gabapentin exposure and lower renal clearance/tubular secretion in individuals carrying this variant
    Variant Name:
    SLC22A4: L305F
    Related Drugs:
    gabapentin
    Evidence:
    PMID:19940846
Variant names are different names that have been used in the literature and other resources to refer to the same variant. Non-curated variant information is accumulated solely by computational methods and has not been verified by the scientific staff at PharmGKB.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ABCB1
  •   
  •   
  • PK
  • FA
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
SLC22A4
  •   
  •   
  • PK
  • FA
  • GN
Publications

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
ADORA1 Uncurated Annotation (source: Drug Bank)
BCAT1 Uncurated Annotation (source: Drug Bank)
CACNA1B Uncurated Annotation (source: Drug Bank)
CACNA2D1 Uncurated Annotation (source: Drug Bank)
CACNA2D2 Uncurated Annotation (source: Drug Bank)

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Not annotated
tamoxifen
  •   
  •   
  •   
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
mephenytoin Uncurated Annotation Increases the effect of hydantoin (source: Drug Bank)
phenytoin Uncurated Annotation Increases the effect of hydantoin (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Epilepsy
  •   
  • PD
  • PK
  • FA
  • GN
Publications, Variants

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00996
KEGG Drug ID:
D00332
PubChem Compound ID:
3446
PubChem Substance ID:
183654

Common Searches

Search PubMed
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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
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