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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 (+)-α-Dihydrotetrabenazine

SMILES

[H][C@]12C[C@@H](O)[C@H](CC(C)C)CN1CCC3=CC(OC)=C(OC)C=C23

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

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
0.97 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
INGREZZA

Cmax

ValueDoseCo-administeredAnalytePopulation
0.19 ng/mL
1 mg single, oral
NBI-98782 plasma
Homo sapiens
39.4 ng/mL
80 mg 1 times / day steady-state, oral
NBI-98782 unknown
Homo sapiens
64 ng/mL
100 mg 1 times / day steady-state, oral
NBI-98782 plasma
Homo sapiens
35.1 ng/mL
50 mg 1 times / day steady-state, oral
NBI-98782 plasma
Homo sapiens
31.7 ng/mL
75 mg single, oral
NBI-98782 plasma
Homo sapiens
56.2 ng/mL
150 mg single, oral
NBI-98782 plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
9.22 ng × h/mL
1 mg single, oral
NBI-98782 plasma
Homo sapiens
695 ng × h/mL
80 mg 1 times / day steady-state, oral
NBI-98782 unknown
Homo sapiens
1110 ng × h/mL
100 mg 1 times / day steady-state, oral
NBI-98782 plasma
Homo sapiens
630 ng × h/mL
50 mg 1 times / day steady-state, oral
NBI-98782 plasma
Homo sapiens
1150 ng × h/mL
75 mg single, oral
NBI-98782 plasma
Homo sapiens
1840 ng × h/mL
150 mg single, oral
NBI-98782 plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
32 h
1 mg single, oral
NBI-98782 plasma
Homo sapiens
18.5 h
80 mg 1 times / day steady-state, oral
NBI-98782 unknown
Homo sapiens
19 h
100 mg 1 times / day steady-state, oral
NBI-98782 plasma
Homo sapiens
21 h
50 mg 1 times / day steady-state, oral
NBI-98782 plasma
Homo sapiens
21 h
75 mg single, oral
NBI-98782 plasma
Homo sapiens
19 h
150 mg single, oral
NBI-98782 plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
36%
80 mg 1 times / day steady-state, oral
NBI-98782 unknown
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

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).