U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C9H17NO2.BrH
Molecular Weight 252.149
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GABAPENTIN HYDROBROMIDE

SMILES

Br.NCC1(CC(O)=O)CCCCC1

InChI

InChIKey=DJOITRXLMIEMFM-UHFFFAOYSA-N
InChI=1S/C9H17NO2.BrH/c10-7-9(6-8(11)12)4-2-1-3-5-9;/h1-7,10H2,(H,11,12);1H

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

Molecular Formula BrH
Molecular Weight 80.912
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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

Curator's Comment: Gabapentin penetrates into the CNS

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.05 µM [Ki]
Target ID: Q8CFG6
Gene ID: 300992.0
Gene Symbol: Cacna2d2
Target Organism: Rattus norvegicus (Rat)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
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
Secondary
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
PubMed

PubMed

TitleDatePubMed
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 Oct
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 Oct
Clinical pharmacokinetics of XP13512, a novel transported prodrug of gabapentin.
2008 Dec
Pharmacokinetics and tolerability of single escalating doses of gabapentin enacarbil: a randomized-sequence, double-blind, placebo-controlled crossover study in healthy volunteers.
2009 Aug
A randomized, double-blind, placebo-controlled, crossover study of XP13512/GSK1838262 in the treatment of patients with primary restless legs syndrome.
2009 Feb
Randomized, double-blind, placebo-controlled study of XP13512/GSK1838262 in patients with RLS.
2009 Feb 3
Gabapentin enacarbil, a gabapentin prodrug for the treatment of the neurological symptoms associated with disorders such as restless legs syndrome.
2009 Jan
Gabapentin enacarbil in restless legs syndrome: a phase 2b, 2-week, randomized, double-blind, placebo-controlled trial.
2009 Nov-Dec
Gabapentin enacarbil (XP13512/GSK1838262) as an alternative treatment to dopaminergic agents for restless legs syndrome.
2010 Aug
The effect of food with varying fat content on the clinical pharmacokinetics of gabapentin after oral administration of gabapentin enacarbil.
2010 Feb
Gabapentin enacarbil in restless legs syndrome.
2010 Jan
Long-term maintenance treatment of restless legs syndrome with gabapentin enacarbil: a randomized controlled study.
2010 Jun
Clinical pharmacokinetic drug interaction studies of gabapentin enacarbil, a novel transported prodrug of gabapentin, with naproxen and cimetidine.
2010 May
Patents

Sample Use Guides

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
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 Sat Dec 16 19:05:54 GMT 2023
Edited
by admin
on Sat Dec 16 19:05:54 GMT 2023
Record UNII
7PXD8ZD6PL
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GABAPENTIN HYDROBROMIDE
Common Name English
CYCLOHEXANEACETIC ACID, 1-(AMINOMETHYL)-, HYDROBROMIDE (1:1)
Systematic Name English
CYCLOHEXANEACETIC ACID, 1-(AMINOMETHYL)-, HYDROBROMIDE
Systematic Name English
2-(1-(AMINOMETHYL)CYCLOHEXYL)ACETICACID,HYDROBROMIDE
Systematic Name English
Code System Code Type Description
PUBCHEM
66875980
Created by admin on Sat Dec 16 19:05:54 GMT 2023 , Edited by admin on Sat Dec 16 19:05:54 GMT 2023
PRIMARY
CAS
797762-15-3
Created by admin on Sat Dec 16 19:05:54 GMT 2023 , Edited by admin on Sat Dec 16 19:05:54 GMT 2023
PRIMARY
FDA UNII
7PXD8ZD6PL
Created by admin on Sat Dec 16 19:05:54 GMT 2023 , Edited by admin on Sat Dec 16 19:05:54 GMT 2023
PRIMARY
EPA CompTox
DTXSID30735939
Created by admin on Sat Dec 16 19:05:54 GMT 2023 , Edited by admin on Sat Dec 16 19:05:54 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY