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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H29NO3
Molecular Weight 319.4385
Optical Activity ( + )
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NBI-98782

SMILES

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

InChI

InChIKey=WEQLWGNDNRARGE-DJIMGWMZSA-N
InChI=1S/C19H29NO3/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/h8-9,12,14,16-17,21H,5-7,10-11H2,1-4H3/t14-,16-,17-/m1/s1

HIDE SMILES / InChI

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).
Name Type Language
NBI-98782
Common Name English
(+)-(2R,3R,11BR)-DIHYDROTETRABENAZINE
Common Name English
2R,3R,11BR)-1,3,4,6,7,11B-HEXAHYDRO-9,10-DIMETHOXY-3-(2-METHYLPROPYL)-2H-BENZO(A)QUINOLIZIN-2-OL
Systematic Name English
(+)-DTBZ
Common Name English
(+)-DIHYDROTETRABENAZINE
Common Name English
Code System Code Type Description
CAS
85081-18-1
Created by admin on Tue Mar 06 10:49:42 UTC 2018 , Edited by admin on Tue Mar 06 10:49:42 UTC 2018
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