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
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
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/21396745https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021894lbl.pdfCurator'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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21396745https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021894lbl.pdf
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.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1893 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21396745 |
36.4 µM [Ki] | ||
Target ID: CHEMBL1893 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21396745 |
54.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | XENAZINE Approved UseTetrabenazine 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 Date2008 |
|||
Primary | XENAZINE Approved UseTetrabenazine 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 Date2008 |
|||
Primary | XENAZINE Approved UseTetrabenazine 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 Date2008 |
|||
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.66 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23339053 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.45 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23339053 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.13 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23339053 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
14% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23339053 |
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
Dose | Population | Adverse 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 Sources: Crisis oculogyric Nausea and vomiting Sweating Sedation Hypotension Confusion Diarrhea Hallucinations Redness Tremor |
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... Other AEs: Depression Sources: Suicidal tendency |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 67, 79 |
inconclusive | |||
Page: 67, 79 |
no | |||
Page: 67, 79 |
no | |||
Page: 67, 79 |
no | |||
Page: 67, 79 |
no | |||
Page: 67, 79 |
no | |||
Page: 67, 79 |
no | |||
Page: 67, 79 |
no | |||
Page: 67, 79 |
no | |||
Page: 67, 79 |
no | |||
Page: 66, 67, 79 |
no | |||
Page: 67, 79 |
no | |||
Page: 67, 79 |
no | |||
Page: 67, 79 |
no | |||
Page: 80.0 |
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 77.0 |
inconclusive | |||
Page: 76.0 |
inconclusive | |||
Page: 76.0 |
inconclusive | |||
Page: 80.0 |
no | no (co-administration study) Comment: tetrabenazine did not affect bioavailability of digoxin Page: 80.0 |
||
Page: 76.0 |
yes | |||
Page: 14, 65, 76 |
yes |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
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Assessment of neuroimaging techniques as biomarkers of the progression of Parkinson's disease. | 2003 Nov |
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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 |
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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 |
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Behavioural effects of thieno and pyrazolo [2,1] benzothiazepine derivatives in mice. | 2004 |
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Dopamine transmission in DYT1 dystonia. | 2004 |
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Adrafinil-induced orofacial dyskinesia. | 2004 Aug |
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[Movement disorders in childhood: therapeutic update]. | 2004 Aug |
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PET studies and physiopathology of motor fluctuations in Parkinson's disease. | 2004 Aug |
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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 |
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Electrochemical monitoring of transport by a vesicular monoamine transporter expressed in Xenopus oocytes. | 2004 Feb 15 |
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Long-term reproducibility of in vivo measures of specific binding of radioligands in rat brain. | 2004 Jul |
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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 |
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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 |
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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 |
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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 |
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Decreased platelet vesicular monoamine transporter density in habitual smokers. | 2005 Mar |
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Decreased platelet vesicular monoamine transporter density in children and adolescents with attention deficit/hyperactivity disorder. | 2005 Mar |
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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 |
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Treatment with the new antipsychotic sertindole for late-occurring undesirable movement effects. | 2005 Nov |
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Platelet vesicular monoamine transporter density in untreated patients diagnosed with social phobia. | 2005 Sep 15 |
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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 |
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Dose-dependent improvement of myoclonic hyperkinesia due to Valproic acid in eight Huntington's Disease patients: a case series. | 2006 Feb 28 |
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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 |
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11634155
Created by
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8A3NP33E5M
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64030
Created by
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1026016-84-1
Created by
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SUBSTANCE RECORD