Gabapentin enacarbil

Identification

Name

Gabapentin enacarbil

Accession Number

DB08872  (DB04922)

Type

Small Molecule

Groups

Approved, Investigational

Description

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

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Gabapentin enacarbil (DB08872)

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Synonyms

• 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
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	Remedy Repack	2016-09-02	Not applicable
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	300 mg/1	Oral	XenoPort Inc.	2013-05-01	2013-04-04

Categories

• Acids, Acyclic
• Amino Acids
• Amino Acids, Peptides, and Proteins
• Aminobutyrates
• Anti-epileptic Agent
• Butyrates
• Central Nervous System Depressants
• Fatty Acids
• Fatty Acids, Volatile
• Lipids

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

• Post-Herpetic Neuralgia (PHN)
• Restless Legs Syndrome (RLS)

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	Human
UVoltage-dependent calcium channel subunit alpha-2/delta-2	Not Available	Human

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

• All Drugs
• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental

Drug	Interaction
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.
3,4-Methylenedioxyamphetamine	The risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Gabapentin enacarbil.
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.
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.

Food Interactions

• No food effects.

References

Synthesis Reference

1. 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

1. 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]
2. 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]
3. 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	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	Active Not Recruiting	Treatment	Irritability / Neurologically Impaired / Pain, Chronic / Signs and Symptoms, Digestive / Sleeplessness	1
2	Completed	Prevention	Migraine Disorders / Migraines	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	Prostate Cancer	1
3	Completed	Treatment	Restless Legs Syndrome (RLS)	6
3	Not Yet 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	Enrolling by Invitation	Treatment	RLS	1
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	1
4	Terminated	Treatment	Restless Legs Syndrome (RLS)	1
Not Available	Active Not Recruiting	Treatment	Restless Legs Syndrome (RLS)	1
Not Available	Recruiting	Not Available	Restless Legs Syndrome (RLS)	1
Not Available	Recruiting	Treatment	Pain NOS	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)
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

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

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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 compoundHydrocarbon derivative / Organic oxide / Organopnictogen compound / Organic oxygen compound / Carbonyl group / Aliphatic homomonocyclic compound

show 6 more

Molecular Framework

Aliphatic homomonocyclic compounds

External Descriptors

carbamate ester, monocarboxylic acid, carboxylic ester, acetal (CHEBI:68840)

Drug created on May 02, 2013 15:20 / Updated on November 02, 2018 06:55