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

Details

Stereochemistry RACEMIC
Molecular Formula C19H27NO3
Molecular Weight 317.4226
Optical Activity ( + / - )
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TETRABENAZINE

SMILES

[H][C@@]12CC(=O)[C@@H](CC(C)C)CN1CCC3=CC(OC)=C(OC)C=C23

InChI

InChIKey=MKJIEFSOBYUXJB-HOCLYGCPSA-N
InChI=1S/C19H27NO3/c1-12(2)7-14-11-20-6-5-13-8-18(22-3)19(23-4)9-15(13)16(20)10-17(14)21/h8-9,12,14,16H,5-7,10-11H2,1-4H3/t14-,16-/m0/s1

HIDE SMILES / InChI

Molecular Formula C19H27NO3
Molecular Weight 317.4226
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including http://reference.medscape.com/drug/xenazine-tetrabenazine-343075 | https://www.drugbank.ca/drugs/DB04844 | https://www.drugs.com/cdi/tetrabenazine.html

Tetrabenazine (trade name Xenazine) is a monoamine depleter and used as the symptomatic treatment of chorea associated with Huntington's disease. Tetrabenazine is a reversible human vesicular monoamine transporter type 2 inhibitor (Ki = 100 nM). It acts within the basal ganglia and promotes depletion of monoamine neurotransmitters serotonin, norepinephrine, and dopamine from stores. It also decreases uptake into synaptic vesicles. Dopamine is required for fine motor movement, so the inhibition of its transmission is efficacious for hyperkinetic movement. Tetrabenazine exhibits weak in vitro binding affinity at the dopamine D2 receptor. The most common adverse reactions, which have occurred in at least 10% of subjects in studies and at least 5% greater than in subjects who received placebo, have been: sedation or somnolence, fatigue, insomnia, depression, suicidal thoughts, akathisia, anxiety, and nausea.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
36.4 µM [Ki]
54.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
XENAZINE

Approved Use

Tetrabenazine tablets are indicated for the treatment of chorea associated with Huntington's disease. Tetrabenazine tablets are a vesicular monoamine transporter 2 (VMAT) inhibitor indicated for the treatment of chorea associated with Huntington's disease. (1)

Launch Date

2008
Primary
XENAZINE

Approved Use

Tetrabenazine tablets are indicated for the treatment of chorea associated with Huntington's disease. Tetrabenazine tablets are a vesicular monoamine transporter 2 (VMAT) inhibitor indicated for the treatment of chorea associated with Huntington's disease. (1)

Launch Date

2008
Primary
XENAZINE

Approved Use

Tetrabenazine tablets are indicated for the treatment of chorea associated with Huntington's disease. Tetrabenazine tablets are a vesicular monoamine transporter 2 (VMAT) inhibitor indicated for the treatment of chorea associated with Huntington's disease. (1)

Launch Date

2008
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.66 ng/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRABENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3.45 ng × h/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRABENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.13 h
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRABENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
14%
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRABENAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1 g single, oral
Overdose
Dose: 1 g
Route: oral
Route: single
Dose: 1 g
Sources:
unknown, adult
n = 8
Health Status: unknown
Age Group: adult
Population Size: 8
Sources:
Other AEs: Acute dystonia, Crisis oculogyric...
Other AEs:
Acute dystonia
Crisis oculogyric
Nausea and vomiting
Sweating
Sedation
Hypotension
Confusion
Diarrhea
Hallucinations
Redness
Tremor
Sources:
12.5 mg 1 times / day steady, oral (starting)
Recommended
Dose: 12.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 12.5 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: Huntington’s disease
Age Group: adult
Sources:
Other AEs: Depression, Suicidal tendency...
AEs

AEs

AESignificanceDosePopulation
Acute dystonia
1 g single, oral
Overdose
Dose: 1 g
Route: oral
Route: single
Dose: 1 g
Sources:
unknown, adult
n = 8
Health Status: unknown
Age Group: adult
Population Size: 8
Sources:
Confusion
1 g single, oral
Overdose
Dose: 1 g
Route: oral
Route: single
Dose: 1 g
Sources:
unknown, adult
n = 8
Health Status: unknown
Age Group: adult
Population Size: 8
Sources:
Crisis oculogyric
1 g single, oral
Overdose
Dose: 1 g
Route: oral
Route: single
Dose: 1 g
Sources:
unknown, adult
n = 8
Health Status: unknown
Age Group: adult
Population Size: 8
Sources:
Diarrhea
1 g single, oral
Overdose
Dose: 1 g
Route: oral
Route: single
Dose: 1 g
Sources:
unknown, adult
n = 8
Health Status: unknown
Age Group: adult
Population Size: 8
Sources:
Hallucinations
1 g single, oral
Overdose
Dose: 1 g
Route: oral
Route: single
Dose: 1 g
Sources:
unknown, adult
n = 8
Health Status: unknown
Age Group: adult
Population Size: 8
Sources:
Hypotension
1 g single, oral
Overdose
Dose: 1 g
Route: oral
Route: single
Dose: 1 g
Sources:
unknown, adult
n = 8
Health Status: unknown
Age Group: adult
Population Size: 8
Sources:
Nausea and vomiting
1 g single, oral
Overdose
Dose: 1 g
Route: oral
Route: single
Dose: 1 g
Sources:
unknown, adult
n = 8
Health Status: unknown
Age Group: adult
Population Size: 8
Sources:
Redness
1 g single, oral
Overdose
Dose: 1 g
Route: oral
Route: single
Dose: 1 g
Sources:
unknown, adult
n = 8
Health Status: unknown
Age Group: adult
Population Size: 8
Sources:
Sedation
1 g single, oral
Overdose
Dose: 1 g
Route: oral
Route: single
Dose: 1 g
Sources:
unknown, adult
n = 8
Health Status: unknown
Age Group: adult
Population Size: 8
Sources:
Sweating
1 g single, oral
Overdose
Dose: 1 g
Route: oral
Route: single
Dose: 1 g
Sources:
unknown, adult
n = 8
Health Status: unknown
Age Group: adult
Population Size: 8
Sources:
Tremor
1 g single, oral
Overdose
Dose: 1 g
Route: oral
Route: single
Dose: 1 g
Sources:
unknown, adult
n = 8
Health Status: unknown
Age Group: adult
Population Size: 8
Sources:
Depression
12.5 mg 1 times / day steady, oral (starting)
Recommended
Dose: 12.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 12.5 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: Huntington’s disease
Age Group: adult
Sources:
Suicidal tendency
12.5 mg 1 times / day steady, oral (starting)
Recommended
Dose: 12.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 12.5 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: Huntington’s disease
Age Group: adult
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive
no
no
no
no
no
no
no
no
no
no
no
no
no
no
Drug as victim
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
[Behavior pharmacology of maprotiline, a new antidepressant].
1975 Nov
Tetrabenazine in the treatment of Huntington's chorea.
1976 Apr 17
Hemiballismus.
2002 Apr
Evaluation of the central properties of several Hypericum species from the Canary Islands.
2002 Dec
[Herpetic encephalitis in childhood: a diagnosis which should not be forgotten].
2002 Feb 16-28
Tetrabenazine fails to antagonize a behavioral effect of cocaine in rhesus monkeys.
2002 Jan-Feb
Experimental conditions for the continuous subcutaneous infusion of four central analgesics in rats.
2002 Jul
Human megakaryocytes cultured in vitro accumulate serotonin but not meta-iodobenzylguanidine whereas platelets concentrate both.
2002 Jun
Chronic clozapine, but not haloperidol, treatment affects rat brain vesicular monoamine transporter 2.
2002 Jun
Effect of tetrabenazine on the striatal uptake of exogenous L-DOPA in vivo: a PET study in young and aged rhesus monkeys.
2002 Jun 15
Methylenedioxymethamphetamine decreases plasmalemmal and vesicular dopamine transport: mechanisms and implications for neurotoxicity.
2002 Mar
Phencyclidine increases vesicular dopamine uptake.
2002 Mar 1
Elevated platelet vesicular monoamine transporter density in untreated patients diagnosed with major depression.
2002 Nov 15
Tetrabenazine treatment for Huntington's disease-associated chorea.
2002 Nov-Dec
Catastrophic reactions induced by tetrabenazine.
2002 Sep
1-(Benzofuran-2-yl)-2-(3,3,3-trifluoropropyl)aminopentane HCl, 3-F-BPAP, antagonizes the enhancer effect of (-)-BPAP in the shuttle box and leaves the effect of (-)-deprenyl unchanged.
2002 Sep 13
Non-synaptic release of [3H]noradrenaline in response to oxidative stress combined with mitochondrial dysfunction in rat hippocampal slices.
2003
Huntington's disease: prospects for neuroprotective therapy 10 years after the discovery of the causative genetic mutation.
2003 Aug
Raclopride studies of dopamine release: dependence on presynaptic integrity.
2003 Dec 1
Self-biting induced by activation of L-type calcium channels in mice: dopaminergic influences.
2003 Jan-Feb
Pharmacological management of tics in patients with TS.
2003 Jul
Obstructive sleep apnea is related to a thalamic cholinergic deficit in MSA.
2003 Jul 8
REM sleep behavior disorder is related to striatal monoaminergic deficit in MSA.
2003 Jul 8
Tetrabenazine in the treatment of severe pediatric chorea.
2003 Jun
Gilles de la Tourette's syndrome.
2003 Mar
Successful therapy of tardive dyskinesia in a 71-year-old woman with a combination of tetrabenazine, olanzapine and tiapride.
2003 Mar
Assessment of neuroimaging techniques as biomarkers of the progression of Parkinson's disease.
2003 Nov
Apparent opposite effects of tetrabenazine and reserpine on the toxic effects of 1-methyl-4-phenylpyridinium or 6-hydroxydopamine on nigro-striatal dopaminergic neurons.
2003 Nov 7
Escalating dose methamphetamine pretreatment alters the behavioral and neurochemical profiles associated with exposure to a high-dose methamphetamine binge.
2003 Oct
Endogenous 5-HT, released by MDMA through serotonin transporter- and secretory vesicle-dependent mechanisms, reduces hippocampal excitatory synaptic transmission by preferential activation of 5-HT1B receptors located on CA1 pyramidal neurons.
2003 Sep
Behavioural effects of thieno and pyrazolo [2,1] benzothiazepine derivatives in mice.
2004
Dopamine transmission in DYT1 dystonia.
2004
[Movement disorders in childhood: therapeutic update].
2004 Aug
Electrochemical monitoring of transport by a vesicular monoamine transporter expressed in Xenopus oocytes.
2004 Feb 15
Long-term reproducibility of in vivo measures of specific binding of radioligands in rat brain.
2004 Jul
Behavioral and neurochemical consequences of long-term intravenous self-administration of MDMA and its enantiomers by rhesus monkeys.
2004 Jul
Striatal monoamine terminals in Lewy body dementia and Alzheimer's disease.
2004 Jun
Identification of tissue-restricted transcripts in human islets.
2004 Oct
Management of the extrapyramidal syndrome in chronic acquired hepatocerebral degeneration (CAHD).
2005 Aug
11C-DTBZ and 18F-FDG PET measures in differentiating dementias.
2005 Jun
Decreased platelet vesicular monoamine transporter density in habitual smokers.
2005 Mar
Pharmacological management of Huntington's disease: an evidence-based review.
2006
Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial.
2006 Feb 14
Tetrabenazine in the treatment of hyperkinetic movement disorders.
2006 Jan
Tetrabenazine versus placebo for chorea in Huntington's disease.
2006 Jul
Longitudinal noninvasive PET-based beta cell mass estimates in a spontaneous diabetes rat model.
2006 Jun
Huntington's Disease.
2006 May
Interaction of amphetamines and related compounds at the vesicular monoamine transporter.
2006 Oct
Positron emission tomography of monoaminergic vesicular binding in aging and Parkinson disease.
2006 Sep
Preparation and evaluation of tetrabenazine enantiomers and all eight stereoisomers of dihydrotetrabenazine as VMAT2 inhibitors.
2011 May
Patents

Sample Use Guides

In Vivo Use Guide
Unknown
Route of Administration: Unknown
In Vitro Use Guide
Unknown
Substance Class Chemical
Created
by admin
on Fri Dec 15 17:17:09 GMT 2023
Edited
by admin
on Fri Dec 15 17:17:09 GMT 2023
Record UNII
Z9O08YRN8O
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TETRABENAZINE
DASH   INN   MART.   MI   ORANGE BOOK   VANDF   WHO-DD  
INN  
Official Name English
2H-BENZO(A)QUINOLIZIN-2-ONE, 1,3,4,6,7,11B-HEXAHYDRO-9,10-DIMETHOXY-3-(2-METHYLPROPYL)-, (3R,11BR)-REL-
Common Name English
RO-1-9569
Code English
TETRABENAZINE [JAN]
Common Name English
RO-19569
Code English
1,3,4,6,7,11B-HEXAHYDRO-3-ISOBUTYL-9,10-DIMETHOXY-2H-BENZO(A)QUINOLIZIN-2-ONE
Common Name English
XENAZINE
Brand Name English
tetrabenazine [INN]
Common Name English
Tetrabenazine [WHO-DD]
Common Name English
TETRABENAZINE [ORANGE BOOK]
Common Name English
TETRABENAZINE [VANDF]
Common Name English
NITOMAN
Brand Name English
TETRABENAZINE [MI]
Common Name English
RO 1-9569
Code English
TETRABENAZINE [MART.]
Common Name English
TETRABENAZINE [USP-RS]
Common Name English
NSC-169886
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 108897
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
FDA ORPHAN DRUG 109797
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
WHO-VATC QN07XX06
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
LIVERTOX NBK548187
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
NDF-RT N0000190856
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
NCI_THESAURUS C471
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
FDA ORPHAN DRUG 278109
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
WHO-ATC N07XX06
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
Code System Code Type Description
MESH
D013747
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
MERCK INDEX
m10596
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY Merck Index
CAS
58-46-8
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
DRUG CENTRAL
2609
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
RXCUI
10390
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY RxNorm
NSC
169886
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
NCI_THESAURUS
C81095
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
DRUG BANK
DB04844
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
SMS_ID
100000092314
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
IUPHAR
4834
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
DAILYMED
Z9O08YRN8O
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
CHEBI
9467
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
EVMPD
SUB10939MIG
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
ECHA (EC/EINECS)
200-383-6
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
ChEMBL
CHEMBL117785
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
WIKIPEDIA
TETRABENAZINE
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
PUBCHEM
11634155
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
RS_ITEM_NUM
1649801
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
EPA CompTox
DTXSID0042614
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
INN
1056
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
NDF-RT
N0000190855
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY Vesicular Monoamine Transporter 2 Inhibitors [MoA]
FDA UNII
Z9O08YRN8O
Created by admin on Fri Dec 15 17:17:09 GMT 2023 , Edited by admin on Fri Dec 15 17:17:09 GMT 2023
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TARGET -> INHIBITOR
EXCRETED UNCHANGED
Unchanged tetrabenazine has not been found in human urine.
URINE
SALT/SOLVATE -> PARENT
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
MINOR
Related Record Type Details
METABOLITE ACTIVE -> PARENT
METABOLITE -> PARENT
METABOLITE ACTIVE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
METABOLITE -> PARENT
Related Record Type Details
ACTIVE MOIETY