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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H27NO3
Molecular Weight 317.4226
Optical Activity UNSPECIFIED
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

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
Tetrabenazine in the treatment of Huntington's chorea.
1976 Apr 17
Adenosine release in morphine-induced hypotension in rats.
1992 Jan
Expression cloning of a reserpine-sensitive vesicular monoamine transporter.
1992 Nov 15
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
Increased ventral striatal monoaminergic innervation in Tourette syndrome.
2003 Aug 12
[11C]DTBZ-PET correlates of levodopa responses in asymmetric Parkinson's disease.
2003 Dec
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
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
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
Adrafinil-induced orofacial dyskinesia.
2004 Aug
[Movement disorders in childhood: therapeutic update].
2004 Aug
PET studies and physiopathology of motor fluctuations in Parkinson's disease.
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
Management of the extrapyramidal syndrome in chronic acquired hepatocerebral degeneration (CAHD).
2005 Aug
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
11C-DTBZ and 18F-FDG PET measures in differentiating dementias.
2005 Jun
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
Decreased platelet vesicular monoamine transporter density in children and adolescents with attention deficit/hyperactivity disorder.
2005 Mar
Antidepressant properties of some Hypericum canariense L. and Hypericum glandulosum Ait. extracts in the forced swimming test in mice.
2005 Mar 21
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
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
Name Type Language
TETRABENAZINE, (-)-
Common Name English
2H-BENZO(A)QUINOLIZIN-2-ONE, 1,3,4,6,7,11B-HEXAHYDRO-9,10-DIMETHOXY-3-(2-METHYLPROPYL)-, (3S,11BS)
Systematic Name English
(3S,11BS)-TETRABENAZINE
Common Name English
(-)-TETRABENAZINE
Common Name English
(-)-TBZ
Common Name English
(3S,11BS)-TBZ
Common Name English
Code System Code Type Description
PUBCHEM
11634155
Created by admin on Sat Dec 16 08:54:11 GMT 2023 , Edited by admin on Sat Dec 16 08:54:11 GMT 2023
PRIMARY
FDA UNII
8A3NP33E5M
Created by admin on Sat Dec 16 08:54:11 GMT 2023 , Edited by admin on Sat Dec 16 08:54:11 GMT 2023
PRIMARY
CHEBI
64030
Created by admin on Sat Dec 16 08:54:11 GMT 2023 , Edited by admin on Sat Dec 16 08:54:11 GMT 2023
PRIMARY
CAS
1026016-84-1
Created by admin on Sat Dec 16 08:54:11 GMT 2023 , Edited by admin on Sat Dec 16 08:54:11 GMT 2023
PRIMARY