Gabapentin

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H17NO2
Molecular Weight	171.2368
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NCC1(CC(O)=O)CCCCC1

InChI

InChIKey=UGJMXCAKCUNAIE-UHFFFAOYSA-N

InChI=1S/C9H17NO2/c10-7-9(6-8(11)12)4-2-1-3-5-9/h1-7,10H2,(H,11,12)

HIDE SMILES / InChI

Molecular Formula	C9H17NO2
Molecular Weight	171.2368
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022399s008lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.xenoport.com/products/regnite/; http://files.shareholder.com/downloads/XNPT/0x0x827504/50A91A4D-7EBD-49B1-9D92-D6D9E100D46A/XNPT_News_2015_5_7_General.pdf; https://www.ncbi.nlm.nih.gov/pubmed/?term=23789956

Gabapentin enacarbil (Horizant in USA, Regnite in Japan), is a prodrug of gabapentin, an antiepileptic drug (AED). It was designed for increased oral bioavailability over gabapentin and to be transported through two high capacity transporters in the intestine, sodium-dependent multivitamin transporter (SMVT) and MCT1. It was shown that the prodrug is a substrate for both MCT1 and SMVT. The oral bioavailability of gabapentin following the administration of its prodrug was found to be 84.2% compared with 25.4% after a similar oral dose of gabapentin. Discovered and developed by XenoPort, gabapentin enacarbil was approved in the United States in 2011 for the treatment of moderate-to-severe primary restless legs syndrome (RLS) in adults and in June 2012 for the management of postherpetic neuralgia (PHN) in adults. Therapeutic effects of gabapentin enacarbil in RLS and PHN are attributable to gabapentin. The precise mechanism by which gabapentin is efficacious in RLS and PHN is unknown. In vitro studies have shown that gabapentin binds with high affinity to certain parts of voltage-activated calcium channels in the central nervous system. However, the relationship of this binding to the therapeutic effects of gabapentin enacarbil in RLS and PHN is unknown. The most common adverse reactions for adult patients with moderate-to-severe primary RLS and PHN receiving Horizant were somnolence/sedation, dizziness, headache, nausea and fatigue.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated calcium channel alpha2/delta subunit 1 19 Target ID: CHEMBL3420 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26234470	Inhibitor 8504		0.05 µM [Ki]
Voltage-dependent calcium channel subunit alpha-2/delta-2 4 Target ID: Q8CFG6 Gene ID: 300992.0 Gene Symbol: Cacna2d2 Target Organism: Rattus norvegicus (Rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26234470	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Restless legs syndrome 17 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022399s008lbl.pdf	Curative		Approved 8583	HORIZANT Approved Use Indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS) in adults, management of postherpetic neuralgia (PHN) in adults. Launch Date 2011
Postherpetic neuralgia 13 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022399s008lbl.pdf	Secondary		Approved 8583	HORIZANT Approved Use Indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS) in adults, management of postherpetic neuralgia (PHN) in adults. Launch Date 2011

C_max

Value	Dose	Co-administered	Analyte	Population
3223.69 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25214768	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		GABAPENTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.98 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9562133	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		GABAPENTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
23574 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25214768	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		GABAPENTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
41.79 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9562133	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		GABAPENTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.69 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/25214768	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		GABAPENTIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:42797	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:42797
ChemicalBook	CB03374713	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB03374713
ChemicalBook	CB3263316	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3263316
eMolecules	538632	https://www.emolecules.com/cgi-bin/more?vid=538632
MolPort	MolPort-000-883-862	https://www.molport.com/shop/molecule-link/MolPort-000-883-862
Selleck Chemicals	Gabapentin(Neurontin)	http://www.selleckchem.com/products/Gabapentin(Neurontin).html
ZINC	ZINC000000004949	http://zinc15.docking.org/substances/ZINC000000004949

PubMed

Title	Date	PubMed
Gabapentin enacarbil (XP13512/GSK1838262) as an alternative treatment to dopaminergic agents for restless legs syndrome.	2010-08	20629607
Long-term maintenance treatment of restless legs syndrome with gabapentin enacarbil: a randomized controlled study.	2010-06	20511481
Clinical pharmacokinetic drug interaction studies of gabapentin enacarbil, a novel transported prodrug of gabapentin, with naproxen and cimetidine.	2010-05	20573085
The effect of food with varying fat content on the clinical pharmacokinetics of gabapentin after oral administration of gabapentin enacarbil.	2010-02	20137764
Gabapentin enacarbil in restless legs syndrome.	2010-01	20200691
Gabapentin enacarbil in restless legs syndrome: a phase 2b, 2-week, randomized, double-blind, placebo-controlled trial.	2009-08-12	19667976
Pharmacokinetics and tolerability of single escalating doses of gabapentin enacarbil: a randomized-sequence, double-blind, placebo-controlled crossover study in healthy volunteers.	2009-08	19808136
Randomized, double-blind, placebo-controlled study of XP13512/GSK1838262 in patients with RLS.	2009-02-03	19188575
A randomized, double-blind, placebo-controlled, crossover study of XP13512/GSK1838262 in the treatment of patients with primary restless legs syndrome.	2009-02	19238802
Gabapentin enacarbil, a gabapentin prodrug for the treatment of the neurological symptoms associated with disorders such as restless legs syndrome.	2009-01	19127491
Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin.	2008-12	18827074
XP13512 [(+/-)-1-([(alpha-isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: II. Improved oral bioavailability, dose proportionality, and colonic absorption compared with gabapentin in rats and monkeys.	2004-10	15146029
XP13512 [(+/-)-1-([(alpha-isobutanoyloxyethoxy)carbonyl] aminomethyl)-1-cyclohexane acetic acid], a novel gabapentin prodrug: I. Design, synthesis, enzymatic conversion to gabapentin, and transport by intestinal solute transporters.	2004-10	15146028

Patents

Sample Use Guides

In Vivo Use Guide

For restless legs syndrome: 600 mg once daily taken at about 5 PM. A dose of 1,200 mg once daily provided no additional benefit compared with the 600-mg dose, but caused an increase in adverse reactions. If the dose is not taken at the recommended time, the next dose should be taken the following day as prescribed. For postherpetic neuralgia: The starting dose is 600 mg in the morning for 3 days, then increase to 600 mg twice daily beginning on day 4. A daily dose greater than 1,200 mg provided no additional benefit. If the dose is not taken at the recommended time, skip this dose, and the next dose should be taken at the time of next scheduled dose.

Route of Administration: Oral

In Vitro Use Guide

MCT-1-mediated transport of XP13512 (gabapentin enacarbil) was evaluated by direct measurement of uptake into X. laevis oocytes expressing human MCT-1. MCT-1-expressing oocytes were incubated with 0.25–1.0 mM XP13512 at room temperature for 5 min. Concentrations of prodrug and gabapentin in cell lysates were determined by LC/MS/MS. XP13512 was taken up by X. laevis oocytes expressing human MCT-1 to a significantly greater extent than uninjected oocytes.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:46:57 GMT 2025` Edited by `admin` on `Mon Mar 31 17:46:57 GMT 2025`
Record UNII	6CW7F3G59X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GRALISE

Preferred Name

English

Gabapentin

Official Name

English

CYCLOHEXANEACETIC ACID, 1-(AMINOMETHYL)-

Common Name

English

gabapentin [INN]

Common Name

English

GABAPENTIN [ORANGE BOOK]

Common Name

English

GABAPENTIN [USP-RS]

Common Name

English

1-(Aminomethyl)cyclohexaneacetic acid

Systematic Name

English

Gabapentin [WHO-DD]

Common Name

English

GABAPENTIN [MART.]

Common Name

English

GABAPENTIN [MI]

Common Name

English

GABAPENTIN [JAN]

Common Name

English

NSC-742194

Code

English

GABAPENTIN [EP IMPURITY]

Common Name

English

NSC-759254

Code

English

GABAPENTIN [USAN]

Common Name

English

GABAPENTIN [HSDB]

Common Name

English

GABAPENTIN [USP MONOGRAPH]

Common Name

English

GABAPENTIN [VANDF]

Common Name

English

GABAPENTIN [EP MONOGRAPH]

Common Name

English

GOE 3450

Code

English

DM-1796

Code

English

CARBATIN

Systematic Name

English

GOE-3450

Code

English

GABAPENTINE

Common Name

English

CI-945

Code

English

Classification Tree Code System Code

WHO-VATC

QN03AX12