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Details

Stereochemistry RACEMIC
Molecular Formula C19H27NO3
Molecular Weight 317.4233
Optical Activity ( + / - )
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TETRABENAZINE

SMILES

CC(C)C[C@@]1([H])CN2CCc3cc(c(cc3[C@]2([H])CC1=O)OC)OC

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 317.4233
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 is used to treat Huntington’s disease symptoms and other hyperkinetic movement disorders. It is sold as the racemate. Tetrabenazine (-) is 8000-fold less potent than Tetrabenazine (+) form in VMAT2 (target) binding assay.

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

1.21875844E12
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

1.21875844E12
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

1.21875844E12
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
Adenosine release in morphine-induced hypotension in rats.
1992 Jan
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
Non-synaptic release of [3H]noradrenaline in response to oxidative stress combined with mitochondrial dysfunction in rat hippocampal slices.
2003
Increased ventral striatal monoaminergic innervation in Tourette syndrome.
2003 Aug 12
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
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
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
Effects of adrenal medulla graft on recovery of GABAergic and dopaminergic neuron deficits in mice: behavioural, pharmacological and immunohistochemical study.
2003 Mar 18
Decreased limbic vesicular monoamine transporter 2 in a genetic rat model of depression.
2003 Mar 7
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
Adrafinil-induced orofacial dyskinesia.
2004 Aug
[Movement disorders in childhood: therapeutic update].
2004 Aug
Differential effects of scopolamine on in vivo binding of dopamine transporter and vesicular monoamine transporter radioligands in rat brain.
2004 Aug
Lack of regional selectivity during the progression of Parkinson disease: implications for pathogenesis.
2004 Dec
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
The effect of rare human sequence variants on the function of vesicular monoamine transporter 2.
2004 Sep
Lobeline analogs with enhanced affinity and selectivity for plasmalemma and vesicular monoamine transporters.
2004 Sep
Tetrabenazine treatment in movement disorders.
2004 Sep-Oct
PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and evidence for presymptomatic compensation.
2005 Dec
The role of radiotracer imaging in Parkinson disease.
2005 Jan 25
The influence of measurement uncertainties on the evaluation of the distribution volume ratio and binding potential in rat studies on a microPET R4: a phantom study.
2005 Jun 21
Decreased platelet vesicular monoamine transporter density in habitual smokers.
2005 Mar
Emerging drugs in Tourette syndrome.
2005 May
Treatment with the new antipsychotic sertindole for late-occurring undesirable movement effects.
2005 Nov
Platelet vesicular monoamine transporter density in untreated patients diagnosed with social phobia.
2005 Sep 15
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
Dose-dependent improvement of myoclonic hyperkinesia due to Valproic acid in eight Huntington's Disease patients: a case series.
2006 Feb 28
Tetrabenazine in the treatment of hyperkinetic movement disorders.
2006 Jan
A blessing in disguise: resolution of tardive dyskinesia with development of cervical myelitis.
2006 Jan
Tetrabenazine versus placebo for chorea in Huntington's disease.
2006 Jul
Measurement of kinetically resolved vesicular dopamine uptake and efflux using rotating disk electrode voltammetry.
2006 Jul 15
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
Patents

Sample Use Guides

The dose of XENAZINE should be individualized. The starting dose should be 12.5 mg per day given once in the morning. After one week, the dose should be increased to 25 mg per day given as 12.5 mg twice a day. XENAZINE should be titrated up slowly at weekly intervals by 12.5 mg, to allow the identification of a dose that reduces chorea and is well tolerated. If a dose of 37.5 to 50 mg per day is needed, it should be given in a three times a day regimen. The maximum recommended single dose is 25 mg. If adverse events such as akathisia, restlessness, parkinsonism, depression, insomnia, anxiety or intolerable sedation occur, titration should be stopped and the dose should be reduced. If the adverse event does not resolve, consideration should be given to withdrawing XENAZINE treatment or initiating other specific treatment (e.g., antidepressants).
Route of Administration: Oral
The brains from male SpragueeDawley rats (approximately 200-225 g weight) (Taconic Labs) were removed, placed on ice, and the striatum was rapidly removed and frozen (-80 C). Thereafter, membranes were prepared by homogenizing striatum samples in 20 volumes (w/v) of ice cold HEPES-sucrose buffer (50 mM HEPES, 0.32 M sucrose, pH adjusted to 8.0) using a Brinkman Polytron (setting 6 for 20 s), and centrifuging them at 20,000xg for 10 min at 4 C. The resulting pellet was resuspended in buffer, recentrifuged and again resuspended in buffer to provide a concentration of 10 mg/mL. Ligand binding experiments were conducted in polystyrene assay tubes containing 0.5 mL HEPES-sucrose buffer for 60 min at room temperature. Each tube contained 2 nM [3H]DHTBZ (specific activity 20 Ci/mmol) (American Radiolabeled Chemicals) and 1.0 mg striatal tissue (original wet weight). Nonspecific binding was determined using 20 mkM(+/-)-TBZ (Tetrabenazine) (Sigma Chemical Co., St Louis, MO). Incubations were terminated by rapid filtration through Whatman GF/B filters, presoaked in 0.5% PEI (polyethyleneimine), using a Brandel R48 filtering manifold (Brandel Instruments Gaithersburg, MD). These filters were then washed twice with 5 mL cold buffer and placed in scintillation vials. Beckman Ready Safe (3.0 mL) was added and the vials were counted the next day using
Substance Class Chemical
Created
by admin
on Sat Jun 26 08:08:36 UTC 2021
Edited
by admin
on Sat Jun 26 08:08:36 UTC 2021
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 [WHO-DD]
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 [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 Sat Jun 26 08:08:37 UTC 2021 , Edited by admin on Sat Jun 26 08:08:37 UTC 2021
FDA ORPHAN DRUG 109797
Created by admin on Sat Jun 26 08:08:37 UTC 2021 , Edited by admin on Sat Jun 26 08:08:37 UTC 2021
WHO-VATC QN07XX06
Created by admin on Sat Jun 26 08:08:38 UTC 2021 , Edited by admin on Sat Jun 26 08:08:38 UTC 2021
LIVERTOX 945
Created by admin on Sat Jun 26 08:08:38 UTC 2021 , Edited by admin on Sat Jun 26 08:08:38 UTC 2021
NDF-RT N0000190856
Created by admin on Sat Jun 26 08:08:38 UTC 2021 , Edited by admin on Sat Jun 26 08:08:38 UTC 2021
NCI_THESAURUS C471
Created by admin on Sat Jun 26 08:08:38 UTC 2021 , Edited by admin on Sat Jun 26 08:08:38 UTC 2021
FDA ORPHAN DRUG 278109
Created by admin on Sat Jun 26 08:08:37 UTC 2021 , Edited by admin on Sat Jun 26 08:08:37 UTC 2021
WHO-ATC N07XX06
Created by admin on Sat Jun 26 08:08:37 UTC 2021 , Edited by admin on Sat Jun 26 08:08:37 UTC 2021
Code System Code Type Description
MESH
D013747
Created by admin on Sat Jun 26 08:08:38 UTC 2021 , Edited by admin on Sat Jun 26 08:08:38 UTC 2021
PRIMARY
MERCK INDEX
M10596
Created by admin on Sat Jun 26 08:08:38 UTC 2021 , Edited by admin on Sat Jun 26 08:08:38 UTC 2021
PRIMARY Merck Index
CAS
58-46-8
Created by admin on Sat Jun 26 08:08:37 UTC 2021 , Edited by admin on Sat Jun 26 08:08:37 UTC 2021
PRIMARY
DRUG CENTRAL
2609
Created by admin on Sat Jun 26 08:08:37 UTC 2021 , Edited by admin on Sat Jun 26 08:08:37 UTC 2021
PRIMARY
RXCUI
10390
Created by admin on Sat Jun 26 08:08:38 UTC 2021 , Edited by admin on Sat Jun 26 08:08:38 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C81095
Created by admin on Sat Jun 26 08:08:38 UTC 2021 , Edited by admin on Sat Jun 26 08:08:38 UTC 2021
PRIMARY
DRUG BANK
DB04844
Created by admin on Sat Jun 26 08:08:37 UTC 2021 , Edited by admin on Sat Jun 26 08:08:37 UTC 2021
PRIMARY
IUPHAR
4834
Created by admin on Sat Jun 26 08:08:37 UTC 2021 , Edited by admin on Sat Jun 26 08:08:37 UTC 2021
PRIMARY
EVMPD
SUB10939MIG
Created by admin on Sat Jun 26 08:08:37 UTC 2021 , Edited by admin on Sat Jun 26 08:08:37 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-383-6
Created by admin on Sat Jun 26 08:08:37 UTC 2021 , Edited by admin on Sat Jun 26 08:08:37 UTC 2021
PRIMARY
ChEMBL
CHEMBL117785
Created by admin on Sat Jun 26 08:08:37 UTC 2021 , Edited by admin on Sat Jun 26 08:08:37 UTC 2021
PRIMARY
WIKIPEDIA
TETRABENAZINE
Created by admin on Sat Jun 26 08:08:38 UTC 2021 , Edited by admin on Sat Jun 26 08:08:38 UTC 2021
PRIMARY
USP_CATALOG
1649801
Created by admin on Sat Jun 26 08:08:38 UTC 2021 , Edited by admin on Sat Jun 26 08:08:38 UTC 2021
PRIMARY USP-RS
EPA CompTox
58-46-8
Created by admin on Sat Jun 26 08:08:37 UTC 2021 , Edited by admin on Sat Jun 26 08:08:37 UTC 2021
PRIMARY
INN
1056
Created by admin on Sat Jun 26 08:08:37 UTC 2021 , Edited by admin on Sat Jun 26 08:08:37 UTC 2021
PRIMARY
NDF-RT
N0000190855
Created by admin on Sat Jun 26 08:08:38 UTC 2021 , Edited by admin on Sat Jun 26 08:08:38 UTC 2021
PRIMARY Vesicular Monoamine Transporter 2 Inhibitors [MoA]
FDA UNII
Z9O08YRN8O
Created by admin on Sat Jun 26 08:08:37 UTC 2021 , Edited by admin on Sat Jun 26 08:08:37 UTC 2021
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