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Details

Stereochemistry RACEMIC
Molecular Formula C19H27NO3.CH4O3S
Molecular Weight 413.528
Optical Activity ( + / - )
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TETRABENAZINE METHANESULFONATE

SMILES

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

InChI

InChIKey=RHDADYXNUCMTQG-DMLYUBSXSA-N
InChI=1S/C19H27NO3.CH4O3S/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;1-5(2,3)4/h8-9,12,14,16H,5-7,10-11H2,1-4H3;1H3,(H,2,3,4)/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

Molecular Formula CH4O3S
Molecular Weight 96.106
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Adenosine release in morphine-induced hypotension in rats.
1992 Jan
Modulation of gastrin processing by vesicular monoamine transporter type 1 (VMAT1) in rat gastrin cells.
1999 Jun 1
Pharmacological options for the treatment of Tourette's disorder.
2001
Decreased densities of dopamine and serotonin transporters and of vesicular monoamine transporter 2 in severely kainic acid lesioned subregions of the striatum.
2001
Vesicular monoamine transporters heterologously expressed in the yeast Saccharomyces cerevisiae display high-affinity tetrabenazine binding.
2001 Feb 9
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
Cocaine-induced increases in vesicular dopamine uptake: role of dopamine receptors.
2001 Sep
Hemiballismus.
2002 Apr
Increased platelet vesicular monoamine transporter density in adult schizophrenia patients.
2002 Aug
Antidepressant effects of the methanol extract of several Hypericum species from the Canary Islands.
2002 Jan
Human megakaryocytes cultured in vitro accumulate serotonin but not meta-iodobenzylguanidine whereas platelets concentrate both.
2002 Jun
Methylenedioxymethamphetamine decreases plasmalemmal and vesicular dopamine transport: mechanisms and implications for neurotoxicity.
2002 Mar
Norepinephrine triggers Ca2+-dependent exocytosis of 5-hydroxytryptamine from rat pinealocytes in culture.
2002 May
Tetrabenazine treatment for Huntington's disease-associated chorea.
2002 Nov-Dec
Methylphenidate redistributes vesicular monoamine transporter-2: role of dopamine receptors.
2002 Oct 1
Catastrophic reactions induced by tetrabenazine.
2002 Sep
Lack of effect of testosterone and dihydrotestosterone compared to 17beta-oestradiol in 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine-mice.
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
VMAT2 binding is elevated in dopa-responsive dystonia: visualizing empty vesicles by PET.
2003 Jul
Tetrabenazine in the treatment of severe pediatric chorea.
2003 Jun
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
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
Dopamine transmission in DYT1 dystonia.
2004
[Movement disorders in childhood: therapeutic update].
2004 Aug
Lack of regional selectivity during the progression of Parkinson disease: implications for pathogenesis.
2004 Dec
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
Lobeline analogs with enhanced affinity and selectivity for plasmalemma and vesicular monoamine transporters.
2004 Sep
Tetrabenazine treatment in movement disorders.
2004 Sep-Oct
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
Antidepressant properties of some Hypericum canariense L. and Hypericum glandulosum Ait. extracts in the forced swimming test in mice.
2005 Mar 21
Pharmacological management of Huntington's disease: an evidence-based review.
2006
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
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
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 Tue Oct 22 05:42:08 UTC 2019
Edited
by admin
on Tue Oct 22 05:42:08 UTC 2019
Record UNII
5X57I1N37U
Record Status Validated (UNII)
Record Version
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Name Type Language
TETRABENAZINE METHANESULFONATE
MI  
Common Name English
TETRABENAZINE MESYLATE
Common Name English
(3R,11BR)-REL-1,3,4,6,7,11B-HEXAHYDRO-9,10-DIMETHOXY-3-(2-METHYLPROPYL)-2H-BENZO(A)QUINOLIZIN-2-ONE METHANESULFONATE
Common Name English
(3R,11BR)-REL-1,3,4,6,7,11B-HEXAHYDRO-9,10-DIMETHOXY-3-(2-METHYLPROPYL)-2H-BENZO(A)QUINOLIZIN-2-ONE METHANESULPHONATE
Common Name English
TETRABENAZINE MESILATE
Common Name English
TETRABENAZINE METHANESULPHONATE
Common Name English
TETRABENAZINE METHANESULFONATE [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C471
Created by admin on Tue Oct 22 05:42:08 UTC 2019 , Edited by admin on Tue Oct 22 05:42:08 UTC 2019
Code System Code Type Description
MERCK INDEX
M10596
Created by admin on Tue Oct 22 05:42:08 UTC 2019 , Edited by admin on Tue Oct 22 05:42:08 UTC 2019
PRIMARY Merck Index
EVMPD
SUB16464MIG
Created by admin on Tue Oct 22 05:42:08 UTC 2019 , Edited by admin on Tue Oct 22 05:42:08 UTC 2019
PRIMARY
PUBCHEM
71586770
Created by admin on Tue Oct 22 05:42:08 UTC 2019 , Edited by admin on Tue Oct 22 05:42:08 UTC 2019
PRIMARY
EPA CompTox
804-53-5
Created by admin on Tue Oct 22 05:42:08 UTC 2019 , Edited by admin on Tue Oct 22 05:42:08 UTC 2019
PRIMARY
CAS
804-53-5
Created by admin on Tue Oct 22 05:42:08 UTC 2019 , Edited by admin on Tue Oct 22 05:42:08 UTC 2019
PRIMARY
NCI_THESAURUS
C97410
Created by admin on Tue Oct 22 05:42:08 UTC 2019 , Edited by admin on Tue Oct 22 05:42:08 UTC 2019
PRIMARY
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