Gabapentin enacarbil is marketed under the name Horizant. It is a prodrug of gabapentin, and indicated in adults for the treatment of Restless Legs Syndrome (RLS) and postherpetic neuralgia (PHN).

Structure

Similar Structures

Synonyms

Gabapentin enacarbil
Gabapentina enacarbilo
Gabapentine enacarbil
Gabapentinum enacarbilum

External IDs

ASP-8825 / ASP8825 / GSK-1838262 / GSK1838262 / XP 13512 / XP-13512 / XP13512

Active Moieties

Name	Kind	UNII	CAS	InChI Key
Gabapentin	prodrug	6CW7F3G59X	60142-96-3	UGJMXCAKCUNAIE-UHFFFAOYSA-N

Product Images

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
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Horizant	Tablet, extended release	300 mg/1	Oral	Glaxosmithkline Inc	2011-12-15	2014-12-05
Horizant	Tablet, extended release	600 mg/1	Oral	Arbor Pharmaceuticals	2013-05-01	Not applicable
Horizant	Tablet, extended release	600 mg/1	Oral	Glaxosmithkline Inc	2011-04-07	2014-07-22
Horizant	Tablet, extended release	300 mg/1	Oral	Arbor Pharmaceuticals	2013-05-01	Not applicable
Horizant	Tablet, extended release	300 mg/1	Oral	XenoPort Inc.	2013-05-01	2013-04-04
Horizant	Tablet, extended release	300 mg/1	Oral	Remedy Repack	2016-09-02	Not applicable

Additional Data Available

Application Number

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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Product Code

A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

UNII

75OCL1SPBQ

CAS number

478296-72-9

Weight

Average: 329.393
Monoisotopic: 329.183837593

Chemical Formula

C₁₆H₂₇NO₆

InChI Key

TZDUHAJSIBHXDL-UHFFFAOYSA-N

InChI

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)

IUPAC Name

2-(1-{[({1-[(2-methylpropanoyl)oxy]ethoxy}carbonyl)amino]methyl}cyclohexyl)acetic acid

SMILES

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

Pharmacology

Indication

For the treatment of adult Restless Legs Syndrome (RLS) and postherpetic neuralgia (PHN).

Associated Conditions

Pharmacodynamics

Since gabapentin enacarbil is a prodrug of gabapentin, it's physiological effects are the same as gabapentin. Concerning PHN, gabapentin prevents allodynia and hyperalgesia.

Mechanism of action

Although the exact mechanism of action of gabapentin in RLS and PHN is unknown, it is presumed to involve the descending noradrenergic system, resulting in the activation of spinal alpha2-adrenergic receptors.

Target	Actions	Organism
UVoltage-dependent calcium channel subunit alpha-2/delta-1	Not Available	Humans
UVoltage-dependent calcium channel subunit alpha-2/delta-2	Not Available	Humans

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Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Gabapentin enacarbil is absorbed in the intestines by active transport through the proton-linked monocarboxylate transporter, MCT-1.

Volume of distribution

The volume of distribution is 76L.

Protein binding

Gabapentin plasma protein binding is less than 3%.

Metabolism

Gabapentin enacarbil does not interact with any of the major cytochrome P450 enzymes.

Route of elimination

Gabapentin enacarbil is eliminated primarily in the urine (94%) and to a lesser extent in the feces (5%).

Half life

The elimination half-life of gabapentin is 5.1 to 6.0 hours.

Clearance

Renal clearance of gabapentin is 5 to 7 L/hr.

Toxicity

Most common adverse reactions are headache, dizziness, and somnolence.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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2,5-Dimethoxy-4-ethylthioamphetamine	The risk or severity of adverse effects can be increased when Gabapentin enacarbil is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamine	The risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Gabapentin enacarbil.
4-Methoxyamphetamine	The risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Gabapentin enacarbil.
5-methoxy-N,N-dimethyltryptamine	The risk or severity of adverse effects can be increased when Gabapentin enacarbil is combined with 5-methoxy-N,N-dimethyltryptamine.
7-Nitroindazole	The risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Gabapentin enacarbil.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline	The risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Gabapentin enacarbil.
Abacavir	Abacavir may decrease the excretion rate of Gabapentin enacarbil which could result in a higher serum level.
Acarbose	Acarbose may decrease the excretion rate of Gabapentin enacarbil which could result in a higher serum level.
Aceclofenac	Aceclofenac may decrease the excretion rate of Gabapentin enacarbil which could result in a higher serum level.
Acemetacin	Acemetacin may decrease the excretion rate of Gabapentin enacarbil which could result in a higher serum level.

Additional Data Available

Extended Description

Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

A severity rating for each drug interaction, from minor to major.

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Evidence Level

A rating for the strength of the evidence supporting each drug interaction.

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Action

An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions

No food effects.

References

Synthesis Reference

Cundy KC, Branch R, Chernov-Rogan T, Dias T, Estrada T, Hold K, Koller K, Liu X, Mann A, Panuwat M, Raillard SP, Upadhyay S, Wu QQ, Xiang JN, Yan H, Zerangue N, Zhou CX, Barrett RW, Gallop MA: 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. J Pharmacol Exp Ther. 2004 Oct;311(1):315-23. Epub 2004 May 14.

General References

Cundy KC, Branch R, Chernov-Rogan T, Dias T, Estrada T, Hold K, Koller K, Liu X, Mann A, Panuwat M, Raillard SP, Upadhyay S, Wu QQ, Xiang JN, Yan H, Zerangue N, Zhou CX, Barrett RW, Gallop MA: 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. J Pharmacol Exp Ther. 2004 Oct;311(1):315-23. Epub 2004 May 14. [PubMed:15146028]
Bialer M: New antiepileptic drugs that are second generation to existing antiepileptic drugs. Expert Opin Investig Drugs. 2006 Jun;15(6):637-47. [PubMed:16732716]
Cundy KC, Annamalai T, Bu L, De Vera J, Estrela J, Luo W, Shirsat P, Torneros A, Yao F, Zou J, Barrett RW, Gallop MA: 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. J Pharmacol Exp Ther. 2004 Oct;311(1):324-33. Epub 2004 May 14. [PubMed:15146029]

External Links

KEGG Drug: D09539
PubChem Compound: 9883933
PubChem Substance: 347827805
ChemSpider: 8059607
ChEBI: 68840
ChEMBL: CHEMBL1628502
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Gabapentin_enacarbil

FDA label

Download (347 KB)

MSDS

Download (30.7 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Not Available	Healthy Volunteers / Pharmacokinetics	1
1	Completed	Treatment	Healthy Volunteers	1
1	Completed	Treatment	Patients With Impaired Renal Function and Haemodialysis	1
1	Completed	Treatment	Restless Legs Syndrome (RLS)	2
1	Withdrawn	Treatment	RLS	1
2	Completed	Prevention	Migraine / Migraine Disorders	1
2	Completed	Treatment	Alcohol Use Disorder (AUD)	1
2	Completed	Treatment	Diabetic Neuropathies	1
2	Completed	Treatment	Postherpetic Neuralgia	2
2	Completed	Treatment	Restless Legs Syndrome (RLS)	3
2	Terminated	Treatment	Diabetic Neuropathies	1
2	Terminated	Treatment	Insomnia / Irritability / Neurologically Impaired / Pain, Chronic / Signs and Symptoms, Digestive	1
2	Terminated	Treatment	Prostate Cancer	1
3	Completed	Treatment	Restless Legs Syndrome (RLS)	6
3	Recruiting	Supportive Care	Cancer of Head and Neck / Narcotic Use	1
4	Completed	Treatment	Postoperative pain	1
4	Completed	Treatment	Restless Legs Syndrome (RLS)	3
4	Not Yet Recruiting	Treatment	Facial Pain / Pain, Acute / Postoperative pain	1
4	Not Yet Recruiting	Treatment	Restless Legs Syndrome (RLS)	1
4	Recruiting	Treatment	Alzheimer's Disease (AD)	1
4	Recruiting	Treatment	RLS	2
4	Terminated	Treatment	Restless Legs Syndrome (RLS)	1
Not Available	Active Not Recruiting	Treatment	Pain	1
Not Available	Completed	Not Available	Restless Legs Syndrome (RLS)	1
Not Available	Completed	Treatment	Restless Legs Syndrome (RLS)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Form	Route	Strength
Tablet, extended release	Oral	300 mg/1
Tablet, extended release	Oral	600 mg/1

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
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US8048917	No	2011-11-01	2022-11-06
US8114909	No	2012-02-14	2026-04-11
US8686034	No	2014-04-01	2025-01-24
US8795725	No	2014-08-05	2029-06-10
US8026279	No	2011-09-27	2026-11-10
US6818787	No	2004-11-16	2022-11-06

Additional Data Available

Filed On

The date on which a patent was filed with the relevant government.

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Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	Melting onset of about 64°C.	From FDA label.
water solubility	Solubility of 0.5 mg/mL in water	From FDA label.
pKa	pKa 5.0	From The Merck Index.

Predicted Properties

Property	Value	Source
Water Solubility	0.325 mg/mL	ALOGPS
logP	2.45	ALOGPS
logP	2.76	ChemAxon
logS	-3	ALOGPS
pKa (Strongest Acidic)	4.35	ChemAxon
pKa (Strongest Basic)	-7.1	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	101.93 Å²	ChemAxon
Rotatable Bond Count	9	ChemAxon
Refractivity	81.69 m³·mol^-1	ChemAxon
Polarizability	34.38 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Taxonomy

Description: This compound belongs to the class of organic compounds known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom.
Kingdom: Organic compounds
Super Class: Organic acids and derivatives
Class: Carboxylic acids and derivatives
Sub Class: Amino acids, peptides, and analogues
Direct Parent: Gamma amino acids and derivatives
Alternative Parents: Dicarboxylic acids and derivatives / Carbamate esters / Organic carbonic acids and derivatives / Carboxylic acid esters / Carboxylic acids / Acetals / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivativesCarbonyl compounds
show 1 more
Substituents: Gamma amino acid or derivatives / Dicarboxylic acid or derivatives / Carbamic acid ester / Carboxylic acid ester / Carbonic acid derivative / Acetal / Carboxylic acid / Organic nitrogen compound / Organonitrogen compound / Organooxygen compound
show 6 more
Molecular Framework: Aliphatic homomonocyclic compounds
External Descriptors: carbamate ester, monocarboxylic acid, carboxylic ester, acetal (CHEBI:68840)

Targets

Details1. Voltage-dependent calcium channel subunit alpha-2/delta-1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Voltage-gated calcium channel activity
Specific Function: The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-...
Gene Name: CACNA2D1
Uniprot ID: P54289
Uniprot Name: Voltage-dependent calcium channel subunit alpha-2/delta-1
Molecular Weight: 124566.93 Da

Details2. Voltage-dependent calcium channel subunit alpha-2/delta-2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Voltage-gated calcium channel activity
Specific Function: The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-t...
Gene Name: CACNA2D2
Uniprot ID: Q9NY47
Uniprot Name: Voltage-dependent calcium channel subunit alpha-2/delta-2
Molecular Weight: 129816.095 Da

Transporters

Details1. Sodium-coupled monocarboxylate transporter 1

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Symporter activity
Specific Function: Acts as an electrogenic sodium (Na(+)) and chloride (Cl-)-dependent sodium-coupled solute transporter, including transport of monocarboxylates (short-chain fatty acids including L-lactate, D-lactat...
Gene Name: SLC5A8
Uniprot ID: Q8N695
Uniprot Name: Sodium-coupled monocarboxylate transporter 1
Molecular Weight: 66577.005 Da

References

Cundy KC, Branch R, Chernov-Rogan T, Dias T, Estrada T, Hold K, Koller K, Liu X, Mann A, Panuwat M, Raillard SP, Upadhyay S, Wu QQ, Xiang JN, Yan H, Zerangue N, Zhou CX, Barrett RW, Gallop MA: 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. J Pharmacol Exp Ther. 2004 Oct;311(1):315-23. Epub 2004 May 14. [PubMed:15146028]

Details2. Sodium-dependent multivitamin transporter

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Sodium-dependent multivitamin transmembrane transporter activity
Specific Function: Transports pantothenate, biotin and lipoate in the presence of sodium.
Gene Name: SLC5A6
Uniprot ID: Q9Y289
Uniprot Name: Sodium-dependent multivitamin transporter
Molecular Weight: 68641.27 Da

References

Cundy KC, Branch R, Chernov-Rogan T, Dias T, Estrada T, Hold K, Koller K, Liu X, Mann A, Panuwat M, Raillard SP, Upadhyay S, Wu QQ, Xiang JN, Yan H, Zerangue N, Zhou CX, Barrett RW, Gallop MA: 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. J Pharmacol Exp Ther. 2004 Oct;311(1):315-23. Epub 2004 May 14. [PubMed:15146028]

Drug created on May 02, 2013 15:20 / Updated on December 02, 2019 08:31

Gabapentin enacarbil

Identification

Structure for Gabapentin enacarbil (DB08872)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

Transporters

References

References