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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

COC1=CC2=C(C=C1OC)[C@@H]3CC(=O)[C@@H](CC(C)C)CN3CC2

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
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
[Behavior pharmacology of maprotiline, a new antidepressant].
1975 Nov
Expression cloning of a reserpine-sensitive vesicular monoamine transporter.
1992 Nov 15
Modulation of gastrin processing by vesicular monoamine transporter type 1 (VMAT1) in rat gastrin cells.
1999 Jun 1
Reversal of tetrabenazine induced depression by selective noradrenaline (norepinephrine) reuptake inhibition.
1999 Oct
Decreased densities of dopamine and serotonin transporters and of vesicular monoamine transporter 2 in severely kainic acid lesioned subregions of the striatum.
2001
Interactions of 1-methyl-4-phenylpyridinium and other compounds with P-glycoprotein: relevance to toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
2001 Aug 10
Vesicular monoamine transporters heterologously expressed in the yeast Saccharomyces cerevisiae display high-affinity tetrabenazine binding.
2001 Feb 9
[Spasmodic torticollis and vertebral hemangioma].
2001 Jan 1-15
Mutagenesis and derivatization of human vesicle monoamine transporter 2 (VMAT2) cysteines identifies transporter domains involved in tetrabenazine binding and substrate transport.
2001 Jul 20
Meige syndrome secondary to basal ganglia injury: a potential cause of acute respiratory distress.
2001 May
Structure-activity studies leading to (-)1-(benzofuran-2-yl)-2-propylaminopentane, ((-)BPAP), a highly potent, selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain.
2001 May
Dyskinesia: L-dopa-induced and tardive dyskinesia.
2001 Nov-Dec
Assessing the integrity of the dopamine system in Parkinson's disease: how best to do it?
2001 Sep
Repetitive administration of tetrabenazine induces irreversible changes in locomotion and morphology of the substantia nigra in rats.
2001 Sep
Cocaine-induced increases in vesicular dopamine uptake: role of dopamine receptors.
2001 Sep
Vesicular neurotransmitter transporters in Huntington's disease: initial observations and comparison with traditional synaptic markers.
2001 Sep 15
Hemiballismus.
2002 Apr
Increased platelet vesicular monoamine transporter density in adult schizophrenia patients.
2002 Aug
Tetrabenazine fails to antagonize a behavioral effect of cocaine in rhesus monkeys.
2002 Jan-Feb
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
Phencyclidine increases vesicular dopamine uptake.
2002 Mar 1
In vivo measures of dopaminergic radioligands in the rat brain: equilibrium infusion studies.
2002 Mar 1
Lack of effect of testosterone and dihydrotestosterone compared to 17beta-oestradiol in 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine-mice.
2002 Sep
Non-synaptic release of [3H]noradrenaline in response to oxidative stress combined with mitochondrial dysfunction in rat hippocampal slices.
2003
Psychopharmacological effects of tianeptine analogous hetero[2,1] benzothiazepine derivatives.
2003
Huntington's disease: prospects for neuroprotective therapy 10 years after the discovery of the causative genetic mutation.
2003 Aug
[11C]DTBZ-PET correlates of levodopa responses in asymmetric Parkinson's disease.
2003 Dec
Classification and treatment of tardive syndromes.
2003 Jan
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
VMAT2 binding is elevated in dopa-responsive dystonia: visualizing empty vesicles by PET.
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
Successful therapy of tardive dyskinesia in a 71-year-old woman with a combination of tetrabenazine, olanzapine and tiapride.
2003 Mar
Decreased limbic vesicular monoamine transporter 2 in a genetic rat model of depression.
2003 Mar 7
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
[Movement disorders in childhood: therapeutic update].
2004 Aug
Electrochemical monitoring of transport by a vesicular monoamine transporter expressed in Xenopus oocytes.
2004 Feb 15
Behavioral and neurochemical consequences of long-term intravenous self-administration of MDMA and its enantiomers by rhesus monkeys.
2004 Jul
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
PET in LRRK2 mutations: comparison to sporadic Parkinson's disease and evidence for presymptomatic compensation.
2005 Dec
11C-DTBZ and 18F-FDG PET measures in differentiating dementias.
2005 Jun
Emerging drugs in Tourette syndrome.
2005 May
Dose-dependent improvement of myoclonic hyperkinesia due to Valproic acid in eight Huntington's Disease patients: a case series.
2006 Feb 28
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
Positron emission tomography of monoaminergic vesicular binding in aging and Parkinson disease.
2006 Sep
Patents

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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 Mon Oct 21 20:32:28 UTC 2019
Edited
by admin
on Mon Oct 21 20:32:28 UTC 2019
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
NSC-169886
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 108897
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
FDA ORPHAN DRUG 109797
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
WHO-VATC QN07XX06
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
LIVERTOX 945
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
NDF-RT N0000190856
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
NCI_THESAURUS C471
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
FDA ORPHAN DRUG 278109
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
WHO-ATC N07XX06
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
Code System Code Type Description
MESH
D013747
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
PRIMARY
MERCK INDEX
M10596
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
PRIMARY Merck Index
CAS
58-46-8
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
PRIMARY
RXCUI
10390
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
PRIMARY RxNorm
NCI_THESAURUS
C81095
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
PRIMARY
DRUG BANK
DB04844
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
PRIMARY
PUBCHEM
11634155
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
PRIMARY
IUPHAR
4834
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
PRIMARY
EVMPD
SUB10939MIG
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
PRIMARY
ECHA (EC/EINECS)
200-383-6
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
PRIMARY
ChEMBL
CHEMBL117785
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
PRIMARY
WIKIPEDIA
TETRABENAZINE
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
PRIMARY
EPA CompTox
58-46-8
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
PRIMARY
INN
1056
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
PRIMARY
NDF-RT
N0000190855
Created by admin on Mon Oct 21 20:32:28 UTC 2019 , Edited by admin on Mon Oct 21 20:32:28 UTC 2019
PRIMARY Vesicular Monoamine Transporter 2 Inhibitors [MoA]
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
ACTIVE MOIETY