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

Details

Stereochemistry RACEMIC
Molecular Formula C16H27NO6
Molecular Weight 329.3893
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GABAPENTIN ENACARBIL

SMILES

CC(C)C(=O)OC(C)OC(=NCC1(CCCCC1)CC(=O)O)O

InChI

InChIKey=TZDUHAJSIBHXDL-UHFFFAOYSA-N
InChI=1S/C16H27NO6/c1-11(2)14(20)22-12(3)23-15(21)17-10-16(9-13(18)19)7-5-4-6-8-16/h11-12H,4-10H2,1-3H3,(H,17,21)(H,18,19)

HIDE SMILES / InChI

Molecular Formula C16H27NO6
Molecular Weight 329.3893
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment:: 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
0.0500000000000000028 µM [Ki]
Target ID: Q8CFG6
Gene ID: 300992
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

1302048000000
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

1302048000000
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
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
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 Jun 26 02:43:44 UTC 2021
Edited
by admin
on Sat Jun 26 02:43:44 UTC 2021
Record UNII
75OCL1SPBQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GABAPENTIN ENACARBIL
DASH   INN   JAN   MART.   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
GABAPENTIN ENACARBIL [MART.]
Common Name English
GSK1838262
Code English
GABAPENTIN ENACARBIL [INN]
Common Name English
GSK-1838262
Common Name English
XP 13512
Code English
GABAPENTIN ENCARBIL [MI]
Common Name English
ASP8825
Code English
XP13512
Code English
CYCLOHEXANEACETIC ACID, 1-((((1-(2-METHYL-1-OXOPROPOXY)ETHOXY)CARBONYL)AMINO)METHYL)-
Common Name English
GABAPENTIN ENACARBIL [WHO-DD]
Common Name English
(1-(((((1RS)-1-((2-METHYLPROPANOYL)OXY)ETHOXY)CARBONYL)AMINO)METHYL)CYCLOHEXYL)ACETIC ACID
Systematic Name English
GABAPENTIN ENACARBIL [ORANGE BOOK]
Common Name English
GABAPENTIN ENACARBIL [JAN]
Common Name English
ASP-8825
Code English
XP-13512
Code English
GABAPENTIN ENACARBIL [USAN]
Common Name English
HORIZANT
Brand Name English
GABAPENTIN ENACARBIL [VANDF]
Common Name English
Classification Tree Code System Code
LIVERTOX 447
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
NCI_THESAURUS C29756
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
FDA ORPHAN DRUG 330710
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
Code System Code Type Description
DRUG CENTRAL
4177
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
PRIMARY
EVMPD
SUB35115
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
PRIMARY
MERCK INDEX
M5619
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
PRIMARY Merck Index
INN
8611
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
PRIMARY
RXCUI
1101333
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
PRIMARY RxNorm
PUBCHEM
9883933
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
PRIMARY
CAS
478296-72-9
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
PRIMARY
IUPHAR
7560
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
PRIMARY
WIKIPEDIA
GABAPENTIN ENACARBIL
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
PRIMARY
ChEMBL
CHEMBL1628502
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
PRIMARY
DRUG BANK
DB08872
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
PRIMARY
NCI_THESAURUS
C79579
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
PRIMARY
FDA UNII
75OCL1SPBQ
Created by admin on Sat Jun 26 02:43:44 UTC 2021 , Edited by admin on Sat Jun 26 02:43:44 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> NON-SUBSTRATE
METABOLIC ENZYME -> NON-SUBSTRATE
ENANTIOMER -> RACEMATE
METABOLIC ENZYME -> NON-SUBSTRATE
METABOLIC ENZYME -> NON-SUBSTRATE
EXCRETED UNCHANGED
URINE
METABOLIC ENZYME -> NON-SUBSTRATE
METABOLIC ENZYME -> NON-SUBSTRATE
ENANTIOMER -> RACEMATE
METABOLIC ENZYME -> NON-SUBSTRATE
Related Record Type Details
METABOLITE ACTIVE -> PRODRUG
Related Record Type Details
ACTIVE MOIETY