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Details

Stereochemistry ABSOLUTE
Molecular Formula C24H38N2O4
Molecular Weight 418.5695
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VALBENAZINE

SMILES

COC1=C(OC)C=C2[C@H]3C[C@@H](OC(=O)[C@@H](N)C(C)C)[C@H](CC(C)C)CN3CCC2=C1

InChI

InChIKey=GEJDGVNQKABXKG-CFKGEZKQSA-N
InChI=1S/C24H38N2O4/c1-14(2)9-17-13-26-8-7-16-10-21(28-5)22(29-6)11-18(16)19(26)12-20(17)30-24(27)23(25)15(3)4/h10-11,14-15,17,19-20,23H,7-9,12-13,25H2,1-6H3/t17-,19-,20-,23+/m1/s1

HIDE SMILES / InChI

Molecular Formula C24H38N2O4
Molecular Weight 418.5695
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

(+)-alpha-Dihydrotetrabenazine (HTBZ) is an active component of tetrabenazine. Tetrabenazine is a mixture of closely-related compounds (isomers) and is readily metabolized in the human body to HTBZ and related isomers. Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorder and is marketed under the trade names Nitoman in Canada and Xenazine in New Zealand and some parts of Europe, and is also available in the USA as an orphan drug. (+)-alpha-Dihydrotetrabenazine and related benzo[a]quinolizines have been labeled with tritium and carbon-11 radioisotopes and used for in vitro and in vivo studies of the VMAT2 in animal and human brain. Adeptio Pharmaceuticals is developing alpha-dihydrotetrabenazine (HTBZ) for the treatment of neurological disorders. It acts by inhibiting vesicular monoamine transporter 2 (VMAT2), thereby blocking the transport of dopamine into axon terminals or into storage vesicles.

CNS Activity

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.97 nM [Ki]
Conditions
PubMed

PubMed

TitleDatePubMed
A ring-closing metathesis-based approach to the synthesis of (+)-tetrabenazine.
2012 Jul 20
Lessons from 11C-dihydrotetrabenazine imaging in a xenograft mouse model of rat insulinoma: is PET imaging of pancreatic beta cell mass feasible?
2017 Dec
Early synaptic dysfunction induced by α-synuclein in a rat model of Parkinson's disease.
2017 Jul 25
Pharmacologic Characterization of Valbenazine (NBI-98854) and Its Metabolites.
2017 Jun
Differences in Dihydrotetrabenazine Isomer Concentrations Following Administration of Tetrabenazine and Valbenazine.
2017 Sep
Patents

Sample Use Guides

In Vivo Use Guide
Single dose administration of (+)-alpha-Dihydrotetrabenazine (HTBZ), escalating dosage amounts 7.5 - 30 mg orally
Route of Administration: Oral
In Vitro Use Guide
(+)-alpha-Dihydrotetrabenazine is a vesicular monoamine transporter (VMAT2) inhibtior with an Ki value of 0.97 nM. IC50 value: 0.97± 0.48 nM. The (+)-isomer showed high affinity in vitro (Ki = 0.97 +/- 0.48 nM) for the vesicular monoamine transporter (VMAT2) in rat brain striatum, whereas the (-)-isomer was inactive (Ki = 2.2 +/- 0.3 uM).
Substance Class Chemical
Created
by admin
on Tue Oct 22 01:50:13 UTC 2019
Edited
by admin
on Tue Oct 22 01:50:13 UTC 2019
Record UNII
54K37P50KH
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
VALBENAZINE
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
MT-5199
Common Name English
NBI-98854
Code English
VALBENAZINE [INN]
Common Name English
VALBENAZINE [WHO-DD]
Common Name English
(2R,3R,11BR)-9,10-DIMETHOXY-3-(2-METHYLPROPYL)-1,3,4,6,7,11B-HEXAHYDRO-2H- BENZO(A)QUINOLIZIN-2-YL L-VALINATE
Common Name English
L-VALINE, (2R,3R,11BR)-1,3,4,6,7,11B-HEXAHYDRO-9,10-DIMETHOXY-3-(2-METHYLPROPYL)-2H-BENZO(A)QUINOLIZIN-2-YL ESTER
Common Name English
VALBENAZINE [USAN]
Common Name English
INGREZZA
Brand Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 608317
Created by admin on Tue Oct 22 01:50:13 UTC 2019 , Edited by admin on Tue Oct 22 01:50:13 UTC 2019
WHO-ATC N07XX13
Created by admin on Tue Oct 22 01:50:13 UTC 2019 , Edited by admin on Tue Oct 22 01:50:13 UTC 2019
NDF-RT N0000190856
Created by admin on Tue Oct 22 01:50:13 UTC 2019 , Edited by admin on Tue Oct 22 01:50:13 UTC 2019
Code System Code Type Description
RXCUI
1918219
Created by admin on Tue Oct 22 01:50:13 UTC 2019 , Edited by admin on Tue Oct 22 01:50:13 UTC 2019
PRIMARY
PUBCHEM
24795069
Created by admin on Tue Oct 22 01:50:13 UTC 2019 , Edited by admin on Tue Oct 22 01:50:13 UTC 2019
PRIMARY
ChEMBL
CHEMBL2364639
Created by admin on Tue Oct 22 01:50:13 UTC 2019 , Edited by admin on Tue Oct 22 01:50:13 UTC 2019
PRIMARY
CAS
1025504-45-3
Created by admin on Tue Oct 22 01:50:13 UTC 2019 , Edited by admin on Tue Oct 22 01:50:13 UTC 2019
PRIMARY
INN
9744
Created by admin on Tue Oct 22 01:50:13 UTC 2019 , Edited by admin on Tue Oct 22 01:50:13 UTC 2019
PRIMARY
EVMPD
SUB182496
Created by admin on Tue Oct 22 01:50:13 UTC 2019 , Edited by admin on Tue Oct 22 01:50:13 UTC 2019
PRIMARY
NCI_THESAURUS
C152815
Created by admin on Tue Oct 22 01:50:13 UTC 2019 , Edited by admin on Tue Oct 22 01:50:13 UTC 2019
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
FECAL
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
VMAT2 inhibitors that cause reversible reduction of dopamine release at the presynaptic nerve terminal by selectively inhibiting presynaptic VMAT2.
BINDING
Ki
SALT/SOLVATE -> PARENT
EXCRETED UNCHANGED
URINE
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
Related Record Type Details
METABOLITE LESS ACTIVE -> PARENT
METABOLITE ACTIVE -> PRODRUG
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC