VIGABATRIN

Details

Stereochemistry	RACEMIC
Molecular Formula	C6H11NO2
Molecular Weight	129.157
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(CCC(O)=O)C=C

InChI

InChIKey=PJDFLNIOAUIZSL-UHFFFAOYSA-N

InChI=1S/C6H11NO2/c1-2-5(7)3-4-6(8)9/h2,5H,1,3-4,7H2,(H,8,9)

HIDE SMILES / InChI

Molecular Formula	C6H11NO2
Molecular Weight	129.157
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.drugbank.ca/drugs/DB01080
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020427s010s011s012,022006s011s012s013lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/22061175

Vigabatrin is an anticonvulsant chemically unrelated to other anticonvulsants. Vigabatrin prevents the catabolism of GABA by irreversibly inhibiting the enzyme GABA transaminase. It is an analog of GABA, but it is not a receptor agonist. However, vigabatrin is not a potent inhibitor of GABA-T with a Ki of 10 mM. Vigabatrin increases brain concentrations of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the CNS, by irreversibly inhibiting enzymes that catabolize GABA (gamma-aminobutyric acid transaminase, GABA-T). Duration of action is determined by rate of GABA-T re-synthesis. Vigabatrin may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. Although administered as a racemic mixture, only the S(+) enantiomer is pharmacologically active. Vigabatrin is sold under the trade name SABRIL, it is indicated as adjunctive therapy for adults and pediatric patients 10 years of age and older with refractory complex partial seizures who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Gamma-amino-N-butyrate transaminase 9 Target ID: CHEMBL2044 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020427s000lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/22061176	Inhibitor 8297		0.85 mM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Epilepsy 121 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020427s000lbl.pdf	Primary		Approved 8429	SABRIL Approved Use SABRIL is an antiepileptic drug (AED) indicated for: • Refractory Complex Partial Seizures in Adults (1.1). It should be used as adjunctive therapy in patients who have responded inadequately to several alternative treatments. Launch Date 2009

C_max

Value	Dose	Co-administered	Analyte	Population
18.4 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8331204/	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		VIGABATRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
73 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8331204/	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		VIGABATRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8331204/	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		VIGABATRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
100% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020427s021,022006s023lbl.pdf	2 g single, oral dose: 2 g route of administration: Oral experiment type: SINGLE co-administered:		VIGABATRIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2 g 1 times / day multiple, oral Highest studied dose Dose: 2 g, 1 times / day Route: oral Route: multiple Dose: 2 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1483856 Page: p.745	unhealthy, 16-63 n = 99 Health Status: unhealthy Condition: Epilepsy Age Group: 16-63 Sex: M+F Population Size: 99 Sources: https://pubmed.ncbi.nlm.nih.gov/1483856 Page: p.745	Disc. AE: Sedation, Seizures... Other AEs: Weight gain, Depression... AEs leading to discontinuation/dose reduction: Sedation (9%) Seizures (2%) Status epilepticus (1%) Other AEs: Weight gain (6%) Depression (1%) Excitability (1%) Itching (1%) Headache (1%) Irritability (1%) Muscle pain (1%) Libido decreased (1%) Sources: https://pubmed.ncbi.nlm.nih.gov/1483856 Page: p.745
2 g 2 times / day multiple, oral Highest studied dose Dose: 2 g, 2 times / day Route: oral Route: multiple Dose: 2 g, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8331204 Page: p.460	healthy, 25.8 ± 8.2 n = 24 Health Status: healthy Age Group: 25.8 ± 8.2 Sex: M Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/8331204 Page: p.460	Sources: https://pubmed.ncbi.nlm.nih.gov/8331204 Page: p.460
4 g single, oral Highest studied dose Dose: 4 g Route: oral Route: single Dose: 4 g Sources: https://pubmed.ncbi.nlm.nih.gov/8331204 Page: p.460	healthy, 27.0 ± 8.2 n = 24 Health Status: healthy Age Group: 27.0 ± 8.2 Sex: M Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/8331204 Page: p.460	Sources: https://pubmed.ncbi.nlm.nih.gov/8331204 Page: p.460
3 g 2 times / day multiple, oral Highest studied dose Dose: 3 g, 2 times / day Route: oral Route: multiple Dose: 3 g, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9924905 Page: p.81	unhealthy, 35 ± 11 n = 41 Health Status: unhealthy Condition: Complex Partial Seizures Age Group: 35 ± 11 Sex: M+F Population Size: 41 Sources: https://pubmed.ncbi.nlm.nih.gov/9924905 Page: p.81	Sources: https://pubmed.ncbi.nlm.nih.gov/9924905 Page: p.81
90 g single, oral (max) Overdose Dose: 90 g Route: oral Route: single Dose: 90 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020427s010s011s012,022006s011s012s013lbl.pdf Page: p.16	unhealthy Health Status: unhealthy Condition: Refractory Complex Partial Seizures Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020427s010s011s012,022006s011s012s013lbl.pdf Page: p.16	Other AEs: Coma, Unconsciousness... Other AEs: Coma (common) Unconsciousness (common) Drowsiness (common) Vertigo (uncommon) Psychosis (uncommon) Apnea (uncommon) Respiratory depression (uncommon) Bradycardia (uncommon) Agitation (uncommon) Irritability (uncommon) Confusion (uncommon) Headache (uncommon) Hypotension (uncommon) Abnormal behavior (uncommon) Seizures (uncommon) Status epilepticus (uncommon) Speech disorder (uncommon) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020427s010s011s012,022006s011s012s013lbl.pdf Page: p.16
1500 mg 2 times / day multiple, oral Recommended Dose: 1500 mg, 2 times / day Route: oral Route: multiple Dose: 1500 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020427s010s011s012,022006s011s012s013lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Refractory Complex Partial Seizures Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020427s010s011s012,022006s011s012s013lbl.pdf Page: p.1	Other AEs: Vision loss, Brain MRI signal changes... Other AEs: Vision loss Brain MRI signal changes Suicidal behavior Suicidal ideation Anemia Somnolence Fatigue Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020427s010s011s012,022006s011s012s013lbl.pdf Page: p.1

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781	inducer 389		inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A 214		CYP2B6 547 CYP2C19 293 CYP3A 129

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/020427s000_ClinPharmR_P1.pdf#page=70 Page: 70.0	likely	weak (co-administration study) Comment: A 16% to 20% average reduction in total phenytoin plasma levels was reported (see label page 21) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/020427s000_ClinPharmR_P1.pdf#page=70 Page: 70.0
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/020427s000_ClinPharmR_P1.pdf#page=70 Page: 70.0	likely	weak (co-administration study) Comment: A 16% to 20% average reduction in total phenytoin plasma levels was reported (see label page 21) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/020427s000_ClinPharmR_P1.pdf#page=70 Page: 70.0
CYP3A 298	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020427s000lbl.pdf#page=22 Page: 22.0	no	no (co-administration study) Comment: No significant difference in pharmacokinetic parameters of vigabatrin were found after treatment with ethinyl estradiol and levonorgestrel; vigabatrin did not interfere significantly with the cytochrome P450 isoenzyme (CYP3A)-mediated metabolism of the contraceptive tested Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020427s000lbl.pdf#page=22 Page: 22.0
CYP3A 298	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020427s000lbl.pdf#page=22 Page: 22.0	no	no (co-administration study) Comment: No significant difference in pharmacokinetic parameters of vigabatrin were found after treatment with ethinyl estradiol and levonorgestrel; vigabatrin did not interfere significantly with the cytochrome P450 isoenzyme (CYP3A)-mediated metabolism of the contraceptive tested Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020427s000lbl.pdf#page=22 Page: 22.0
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/020427s000_ClinPharmR_P1.pdf#page=70 Page: 70.0	not significant
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/020427s000_ClinPharmR_P1.pdf#page=70 Page: 70.0	not significant

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022006s000_ClinPharm.pdf#page=4 Page: 4.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63638	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63638
ChemicalBook	CB1285620	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1285620
MolPort	MolPort-003-666-796	https://www.molport.com/shop/molecule-link/MolPort-003-666-796
eMolecules	595429	https://www.emolecules.com/cgi-bin/more?vid=595429

PubMed

Title	Date	PubMed
Visual dysfunction in patients receiving vigabatrin: clinical and electrophysiologic findings.	1999 Dec 10	10599785
Synergistic neurotoxicity by human immunodeficiency virus proteins Tat and gp120: protection by memantine.	2000 Feb	10665489
Another case of reversibility of visual-field defect induced by vigabatrin monotherapy: is young age a favorable factor?	2000 Jun	11076009
Psychiatric symptoms after therapy with new antiepileptic drugs: psychopathological and seizure related variables.	2000 Jun	10880283
Effect of long-term vigabatrin administration on the immature rat brain.	2000 Jun	10840396
[[Acute encephalopathy and myoclonic status induced by vigabatrin monotherapy] ].	2000 Oct	11143506
A risk-benefit assessment of treatments for infantile spasms.	2001	11665869
The management of refractory idiopathic epilepsies.	2001	11520320
Epileptic encephalopathy.	2001	11520318
GABAergic mechanisms in epilepsy.	2001	11520315
The effect of gamma-vinyl-GABA on the consumption of concurrently available oral cocaine and ethanol in the rat.	2001 Feb	11267634
Progress report on new antiepileptic drugs: a summary of the Fifth Eilat Conference (EILAT V).	2001 Jan	11137386
Revised guideline for prescribing vigabatrin in children. Guideline's claim about infantile spasms is not based on appropriate evidence.	2001 Jan 27	11159628
[Vigabatrin and visual fields defects].	2001 Jan 8	11379251
Gabapentin but not vigabatrin is effective in the treatment of acquired nystagmus in multiple sclerosis: How valid is the GABAergic hypothesis?	2001 Jul	11413274
[Social and economic aspects of administration of new antiepileptic drugs].	2001 Mar-Apr	11599223
West syndrome and other infantile epileptic encephalopathies--Indian hospital experience.	2001 Nov	11701262
West syndrome: a university hospital based study from Oman.	2001 Nov	11701261
National survey of West syndrome in Taiwan.	2001 Nov	11701257
National survey on West syndrome in Korea.	2001 Nov	11701256
Gamma vinyl-GABA differentially modulates NMDA antagonist-induced increases in mesocortical versus mesolimbic DA transmission.	2001 Nov	11682254
Vigabatrin protects against hippocampal damage but is not antiepileptogenic in the lithium-pilocarpine model of temporal lobe epilepsy.	2001 Nov	11673025
Pharmacologic rescue of lethal seizures in mice deficient in succinate semialdehyde dehydrogenase.	2001 Oct	11544478
Gamma-vinyl GABA (GVG) blocks expression of the conditioned place preference response to heroin in rats.	2001 Sep 1	11391783

Patents

Sample Use Guides

In Vivo Use Guide

Refractory Complex Partial Seizures Adults >16 years of age: Initiate therapy at 500 mg twice daily, increasing total daily dose per instructions. The recommended dose is 1500 mg twice daily (2.2). Pediatrics 10 to 16 years of age: Treatment is based on body weight. Initiate therapy at 250 mg twice daily, increasing total daily dose per instructions. The recommended maintenance dose is 1000 mg twice daily. Patients weighing more than 60 kg should be dosed according to adult recommendations (2.2). Infantile Spasms Initiate therapy at 50 mg/kg/day given in 2 divided doses increasing total daily dose per instructions to a maximum of 150 mg/kg/day given in 2 divided doses (2.3). Given orally with or without food.

Route of Administration: Oral

In Vitro Use Guide

Vigabatrin inhibits the uptake of taurine in Caco-2 and MDCK cells to 34 ± 3 and 53 ± 2%, respectively, at a concentration of 30 mM.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:58:39 GMT 2023` Edited by `admin` on `Fri Dec 15 16:58:39 GMT 2023`
Record UNII	GR120KRT6K
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VIGABATRIN

Official Name

English

Vigabatrin [WHO-DD]

Common Name

English

4-Amino-5-hexenoic acid

Systematic Name

English

GAMMA-VINYL GABA

Common Name

English

vigabatrin [INN]

Common Name

English

VIGABATRIN [USP MONOGRAPH]

Common Name

English

VINYL GAMMA-AMINOBUTYRIC ACID

Systematic Name

English

VIGABATRIN [USAN]

Common Name

English

VIGABATRIN [ORANGE BOOK]

Common Name

English

VIGABATRIN, (±)-

Common Name

English

VIGABATRIN [MART.]

Common Name

English

VIGABATRIN [EP MONOGRAPH]

Common Name

English

VIGABATRIN [JAN]

Common Name

English

5-HEXENOIC ACID, 4-AMINO-

Common Name

English

MDL 71,754

Code

English

RMI-71754

Code

English

SABRIL

Brand Name

English

CPP-109

Code

English

GAMMA VINYL GABA

Common Name

English

VIGABATRIN [USP-RS]

Common Name

English

MDL-71754

Code

English

VIGABATRIN [VANDF]

Common Name

English

VIGABATRIN [MI]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

609817