tetrabenazine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
2609 58-46-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • choreazine
  • tetrabenazine
  • (+/-)-Tetrabenazine
  • rubigen
A drug formerly used as an antipsychotic and treatment of various movement disorders. Tetrabenazine blocks neurotransmitter uptake into adrenergic storage vesicles and has been used as a high affinity label for the vesicle transport system.
  • Molecular weight: 317.43
  • Formula: C19H27NO3
  • CLOGP: 3.27
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 0
  • TPSA: 38.77
  • ALOGS: -2.94
  • ROTB: 4
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.10 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Bocci G, Oprea TI, Benet LZ
EoM (Fraction excreted unchanged in urine) 0 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 45.00 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 5 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
S (Water solubility) 0.34 mg/mL Bocci G, Oprea TI, Benet LZ
fu (Fraction unbound in plasma) 0.14 % Kawashima H, Watanabe R, Esaki T, Kuroda M, Nagao C, Natsume-Kitatani Y, Ohashi R, Komura H, Mizuguchi K

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.013 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.059 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 38.194 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 37.757 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 13.380 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 28.470 % High 1
herg hERG pIC50 4.899 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 15.740 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 143.549 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 9.960 % High 1
kinase-safety-class ACVR2A,ACVR2B,AKT2,AKT3,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,GSK3B,ITK,JAK2,JAK3,MAP3K21,MAP3K7,MAPK10,MAPK7,MAPK9,MAPKAPK2,MET,MTOR,NTRK2,PDK2,PDK4,PDPK1,PIK3CB,PIM2,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TGFBR1,TTK,ZAP70 48
kinase-selectivity-class AXL,EIF2AK3,GRK2 3
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.729 High 1
mh-clint Mouse hepatocyte intrinsic clearance 97.949 High 1
mppb Mouse plasma protein binding (% unbound) 12.180 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 2.472 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 0 High 1
pppb Pig plasma protein binding (% unbound) 25.610 % High 1
rh-clint Rat hepatocyte intrinsic clearance 177.419 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 62.670 % High 1
rppb Rat plasma protein binding (% unbound) 11.440 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 270.396 uM High 1

Approvals:

DateAgencyCompanyOrphan
Aug. 15, 2008 FDA VALEANT PHARMS NORTH

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Death 605.85 34.04 332 3989 456219 90167907
Depression 218.71 34.04 150 4171 300451 90323675
Parkinsonism 170.87 34.04 51 4270 14014 90610112
Dyskinesia 126.64 34.04 52 4269 36482 90587644
Tardive dyskinesia 121.40 34.04 37 4284 10893 90613233
Off label use 108.98 34.04 190 4131 1102062 89522064
Somnolence 97.15 34.04 80 4241 209004 90415122
Hospitalisation 88.16 34.04 62 4259 128038 90496088
Dysphagia 83.49 34.04 57 4264 112221 90511905
Product administration error 82.75 34.04 35 4286 26388 90597738
Suicidal ideation 81.15 34.04 48 4273 73807 90550319
Huntington's disease 80.57 34.04 9 4312 0 90624126
Crying 70.55 34.04 31 4290 25614 90598512
Tremor 67.71 34.04 57 4264 153116 90471010
Drug ineffective for unapproved indication 64.65 34.04 40 4281 66604 90557522
Fall 52.30 34.04 87 4234 481723 90142403
Hospice care 52.09 34.04 19 4302 9685 90614441
Aggression 47.84 34.04 24 4297 26644 90597482
Tic 46.67 34.04 12 4309 1899 90622227
Movement disorder 45.92 34.04 24 4297 28995 90595131
Abnormal behaviour 45.46 34.04 22 4299 22606 90601520
Insomnia 44.14 34.04 66 4255 333408 90290718
Akathisia 42.46 34.04 17 4304 11142 90612984
Dystonia 41.98 34.04 19 4302 16800 90607326
Product substitution issue 40.74 34.04 19 4302 17989 90606137
Anxiety 40.54 34.04 61 4260 309711 90314415
Anger 39.07 34.04 17 4304 13703 90610423
Pneumonia aspiration 38.23 34.04 24 4297 40916 90583210
Sedation 37.04 34.04 25 4296 48146 90575980
Agitation 36.01 34.04 28 4293 67070 90557056

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Death 257.15 36.32 235 2884 470950 42147266
Dystonia 107.63 36.32 39 3080 12751 42605465
Depression 104.85 36.32 77 3042 111286 42506930
Prescribed overdose 85.33 36.32 33 3086 12894 42605322
Tic 84.68 36.32 22 3097 2361 42615855
Suicidal ideation 81.20 36.32 48 3071 48113 42570103
Off label use 73.46 36.32 150 2969 638185 41980031
Tardive dyskinesia 73.07 36.32 25 3094 6899 42611317
Chorea 69.52 36.32 17 3102 1427 42616789
Anxiety 67.09 36.32 61 3058 118499 42499717
Somnolence 63.54 36.32 64 3055 141041 42477175
Hospitalisation 57.91 36.32 46 3073 74284 42543932
Drug ineffective for unapproved indication 52.73 36.32 36 3083 46127 42572089
Parkinsonism 52.39 36.32 22 3097 10601 42607615
Sedation 50.33 36.32 30 3089 30445 42587771
Drug ineffective 49.89 36.32 128 2991 630069 41988147
Impulsive behaviour 47.36 36.32 14 3105 2411 42615805
Dyskinesia 47.22 36.32 27 3092 25363 42592853
Torticollis 45.54 36.32 12 3107 1358 42616858
Sedation complication 44.80 36.32 14 3105 2905 42615311
Neuroleptic malignant syndrome 43.08 36.32 24 3095 21448 42596768
Hypoventilation 41.17 36.32 14 3105 3788 42614428
Investigation 39.93 36.32 10 3109 925 42617291
Huntington's disease 38.67 36.32 6 3113 42 42618174
Depressed mood 38.55 36.32 23 3096 23361 42594855
Aggression 37.97 36.32 29 3090 44134 42574082

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Death 493.41 32.33 311 3853 698558 109886577
Off label use 178.40 32.33 247 3917 1499938 109085197
Parkinsonism 159.83 32.33 51 4113 22136 110562999
Tardive dyskinesia 152.76 32.33 44 4120 13535 110571600
Dystonia 113.60 32.33 41 4123 25764 110559371
Drug ineffective for unapproved indication 97.81 32.33 56 4108 102782 110482353
Drug ineffective 92.45 32.33 186 3978 1520354 109064781
Dyskinesia 92.44 32.33 43 4121 51403 110533732
Suicidal ideation 86.24 32.33 50 4114 93887 110491248
Hospitalisation 85.77 32.33 58 4106 142435 110442700
Tic 70.71 32.33 18 4146 3475 110581660
Somnolence 69.90 32.33 70 4094 297379 110287756
Depression 67.90 32.33 71 4093 317264 110267871
Prescribed overdose 65.80 32.33 41 4123 87540 110497595
Neuroleptic malignant syndrome 56.63 32.33 27 4137 34032 110551103
Product administration error 54.36 32.33 27 4137 37190 110547945
Sedation 53.29 32.33 33 4131 69650 110515485
Investigation 52.08 32.33 13 4151 2319 110582816
Akathisia 45.98 32.33 19 4145 17094 110568041
Depressed mood 44.48 32.33 28 4136 60781 110524354
Impulsive behaviour 42.93 32.33 12 4152 3303 110581832
Hypoventilation 39.93 32.33 14 4150 8067 110577068
Pneumonia aspiration 39.37 32.33 29 4135 81204 110503931
Anxiety 39.03 32.33 56 4108 345022 110240113
Dysphagia 37.57 32.33 37 4127 153563 110431572
Sedation complication 33.79 32.33 16 4148 19839 110565296

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N07XX06 NERVOUS SYSTEM
OTHER NERVOUS SYSTEM DRUGS
OTHER NERVOUS SYSTEM DRUGS
Other nervous system drugs
MeSH PA D014179 Neurotransmitter Uptake Inhibitors
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018663 Adrenergic Agents
MeSH PA D018759 Adrenergic Uptake Inhibitors
MeSH PA D049990 Membrane Transport Modulators
FDA MoA N0000190855 Vesicular Monoamine Transporter 2 Inhibitors
FDA EPC N0000190856 Vesicular Monoamine Transporter 2 Inhibitor
CHEBI has role CHEBI:35476 antipsychotic agent
CHEBI has role CHEBI:35640 adrenergic uptake inhibitor

Related Drugs by ATC class:

N07XX Other nervous system drugs 23 drugs
amifampridinearimoclomoldeutetrabenazinedextromethorphanedaravoneeplontersenfampridineinotersen laquinimodlevacetylleucineomaveloxolonepatisiran show all 23 →

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Huntington's chorea indication 58756001 DOID:12858
Suicidal thoughts contraindication 6471006
Mood swings contraindication 18963009
Feeling agitated contraindication 24199005
Orthostatic hypotension contraindication 28651003
Torsades de pointes contraindication 31722008
Parkinsonism contraindication 32798002
Depressive disorder contraindication 35489007
Dysphagia contraindication 40739000
Low blood pressure contraindication 45007003
Tardive dyskinesia contraindication 102449007
Prolonged QT interval contraindication 111975006
Disease of liver contraindication 235856003 DOID:409
Hyperprolactinemia contraindication 237662005 DOID:12700
Suicidal contraindication 267073005
Akathisia contraindication 285145004
Severe depression contraindication 310497006
Impaired cognition contraindication 386806002
Poor metabolizer due to cytochrome p450 CYP2D6 variant contraindication 423629005
Congenital long QT syndrome contraindication 442917000




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.01 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Synaptic vesicular amine transporter Transporter INHIBITOR Ki 7 WOMBAT-PK CHEMBL
Alpha-2A adrenergic receptor GPCR Ki 6.02 WOMBAT-PK
Alpha-2C adrenergic receptor GPCR Ki 5.89 WOMBAT-PK
Chromaffin granule amine transporter Transporter INHIBITOR Ki 4.70 IUPHAR
D(2) dopamine receptor GPCR Ki 5.68 WOMBAT-PK
Sodium channel alpha subunits; brain (Types I, II, III) Ion channel IC50 4.07 CHEMBL
Synaptic vesicular amine transporter Transporter Ki 8.40 CHEMBL
Synaptic vesicular amine transporter Transporter Ki 8.12 CHEMBL

External reference:

IDSource
4027903 VUID
N0000177920 NUI
D08575 KEGG_DRUG
4027903 VANDF
C0039623 UMLSCUI
CHEBI:9467 CHEBI
YHL PDB_CHEM_ID
CHEMBL117785 ChEMBL_ID
DB04844 DRUGBANK_ID
D013747 MESH_DESCRIPTOR_UI
6018 PUBCHEM_CID
4834 IUPHAR_LIGAND_ID
1056 INN_ID
Z9O08YRN8O UNII
10390 RXNORM
16831 MMSL
63336 MMSL
d04597 MMSL
003767 NDDF
323260004 SNOMEDCT_US
363581004 SNOMEDCT_US
14580381 PUBCHEM_CID
Z9O08YRN8O INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Tetrabenazine HUMAN PRESCRIPTION DRUG LABEL 1 23155-938 TABLET 12.50 mg oral ANDA 20 sections
Tetrabenazine HUMAN PRESCRIPTION DRUG LABEL 1 23155-939 TABLET 25 mg ORAL ANDA 20 sections
Tetrabenazine Human Prescription Drug Label 1 27241-176 TABLET 12.50 mg ORAL ANDA 30 sections
Tetrabenazine Human Prescription Drug Label 1 27241-177 TABLET 25 mg ORAL ANDA 30 sections
Tetrabenazine Human Prescription Drug Label 1 31722-821 TABLET, COATED 12.50 mg ORAL ANDA 31 sections
Tetrabenazine Human Prescription Drug Label 1 31722-822 TABLET, COATED 25 mg ORAL ANDA 31 sections
Tetrabenazine HUMAN PRESCRIPTION DRUG LABEL 1 43598-394 TABLET 12.50 mg ORAL ANDA 30 sections
Tetrabenazine HUMAN PRESCRIPTION DRUG LABEL 1 43598-395 TABLET 25 mg ORAL ANDA 30 sections
Tetrabenazine Human Prescription Drug Label 1 47335-179 TABLET 25 mg ORAL ANDA 30 sections
Tetrabenazine Human Prescription Drug Label 1 47335-277 TABLET 12.50 mg ORAL ANDA 30 sections
Tetrabenazine HUMAN PRESCRIPTION DRUG LABEL 1 51407-480 TABLET 12.50 mg ORAL ANDA 32 sections
Tetrabenazine HUMAN PRESCRIPTION DRUG LABEL 1 51407-481 TABLET 25 mg ORAL ANDA 32 sections
Tetrabenazine HUMAN PRESCRIPTION DRUG LABEL 1 60505-3882 TABLET 12.50 mg ORAL ANDA 32 sections
Tetrabenazine HUMAN PRESCRIPTION DRUG LABEL 1 60505-3883 TABLET 25 mg ORAL ANDA 32 sections
Xenazine HUMAN PRESCRIPTION DRUG LABEL 1 67386-421 TABLET 12.50 mg ORAL NDA 31 sections
Xenazine HUMAN PRESCRIPTION DRUG LABEL 1 67386-422 TABLET 25 mg ORAL NDA 31 sections
Tetrabenazine HUMAN PRESCRIPTION DRUG LABEL 1 68094-805 TABLET 25 mg ORAL ANDA 32 sections
Tetrabenazine HUMAN PRESCRIPTION DRUG LABEL 1 68094-905 TABLET 12.50 mg ORAL ANDA 32 sections
tetrabenazine HUMAN PRESCRIPTION DRUG LABEL 1 68682-421 TABLET 12.50 mg ORAL NDA authorized generic 31 sections
tetrabenazine HUMAN PRESCRIPTION DRUG LABEL 1 68682-422 TABLET 25 mg ORAL NDA authorized generic 31 sections
TETRABENAZINE HUMAN PRESCRIPTION DRUG LABEL 1 69452-117 TABLET 12.50 mg ORAL ANDA 20 sections
TETRABENAZINE HUMAN PRESCRIPTION DRUG LABEL 1 69452-118 TABLET 25 mg ORAL ANDA 20 sections
tetrabenazine HUMAN PRESCRIPTION DRUG LABEL 1 70436-101 TABLET 12.50 mg ORAL ANDA 31 sections
tetrabenazine HUMAN PRESCRIPTION DRUG LABEL 1 70436-102 TABLET 25 mg ORAL ANDA 31 sections