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
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)
Molecular Formula | C9H17NO2 |
Molecular Weight | 171.2368 |
Charge | 0 |
Count |
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Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator'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
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=7693432
Curator's Comment: Gabapentin penetrates into the CNS
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3420 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26234470 |
0.05 µM [Ki] | ||
Target ID: Q8CFG6 Gene ID: 300992.0 Gene Symbol: Cacna2d2 Target Organism: Rattus norvegicus (Rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/26234470 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Curative | HORIZANT Approved UseIndicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS)
in adults, management of postherpetic neuralgia (PHN) in adults. Launch Date2011 |
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Secondary | HORIZANT Approved UseIndicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS)
in adults, management of postherpetic neuralgia (PHN) in adults. Launch Date2011 |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
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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 |
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A randomized, double-blind, placebo-controlled, crossover study of XP13512/GSK1838262 in the treatment of patients with primary restless legs syndrome. | 2009 Feb |
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Gabapentin enacarbil in restless legs syndrome: a phase 2b, 2-week, randomized, double-blind, placebo-controlled trial. | 2009 Nov-Dec |
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Gabapentin enacarbil (XP13512/GSK1838262) as an alternative treatment to dopaminergic agents for restless legs syndrome. | 2010 Aug |
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Gabapentin enacarbil in restless legs syndrome. | 2010 Jan |
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Long-term maintenance treatment of restless legs syndrome with gabapentin enacarbil: a randomized controlled study. | 2010 Jun |
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Clinical pharmacokinetic drug interaction studies of gabapentin enacarbil, a novel transported prodrug of gabapentin, with naproxen and cimetidine. | 2010 May |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15146029
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
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on
Edited
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Record UNII |
6CW7F3G59X
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Record Status |
Validated (UNII)
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Record Version |
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WHO-VATC |
QN03AX12
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WHO-ATC |
N03AX12
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FDA ORPHAN DRUG |
236506
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NDF-RT |
N0000008486
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NDF-RT |
N0000175753
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FDA ORPHAN DRUG |
88695
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NCI_THESAURUS |
C29756
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LIVERTOX |
NBK548252
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AA-108
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6CW7F3G59X
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C040029
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100000092663
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m5618
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5483
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C1108
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60142-96-3
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DB00996
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25480
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1287303
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759254
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42797
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CHEMBL940
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Gabapentin
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GABAPENTIN
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Related Record | Type | Details | ||
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SALT/SOLVATE -> PARENT | |||
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (HPLC)
USP
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SALT/SOLVATE -> PARENT |
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TRANSPORTER -> SUBSTRATE | |||
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (HPLC)
EP
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TRANSPORTER -> SUBSTRATE |
CLINICALLY SIGNIFICANT
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BINDER->LIGAND |
BINDING
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TARGET->LIGAND |
Related Record | Type | Details | ||
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PRODRUG -> METABOLITE ACTIVE |
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Related Record | Type | Details | ||
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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RENAL IMPAIRMENT PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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IMMEDIATE-RELEASE PHARMACOKINETIC |
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ORAL BIOAVAILABILITY | PHARMACOKINETIC |
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MAXIMUM TOLERATED DOSE | TOXICITY |
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