?-Dihydrotetrabenazine

Details

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

SHOW SMILES / InChI

Structure Search

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

Molecular Formula	C19H29NO3
Molecular Weight	319.4385
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9094204 | http://adisinsight.springer.com/drugs/800046946

(+)-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 Target	Pharmacology	Condition	Potency
Synaptic vesicular amine transporter 57 Target ID: CHEMBL4828 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9094204 \| https://www.ncbi.nlm.nih.gov/pubmed/19632829	Inhibitor 8504		0.97 nM [Ki]
Synaptic vesicular amine transporter 57 Target ID: Q05940 Gene ID: 6571.0 Gene Symbol: SLC18A2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/30160230	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Neurological disorders 10 Sources: http://adisinsight.springer.com/drugs/800046946	Primary		Phase I 438	Unknown Approved Use Unknown
tardive dyskinesia 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf	Primary		Approved 8583	INGREZZA Approved Use INGREZZA is indicated for the treatment of adults with tardive dyskinesia Launch Date 2017

C_max

Value	Dose	Analyte	Population
0.19 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
31.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
56.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
35.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
64 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
39.4 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241oirg1s000clinpharmr.pdf	80 mg 1 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 unknown	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
9.22 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1150 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1840 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
630 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1110 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
695 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241oirg1s000clinpharmr.pdf	80 mg 1 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 unknown	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
32 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
21 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
19 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
21 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
19 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28839339/	100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
18.5 h OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241oirg1s000clinpharmr.pdf	80 mg 1 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	NBI-98782 unknown	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
36% OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241oirg1s000clinpharmr.pdf	80 mg 1 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		NBI-98782 unknown	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf	unhealthy, 18 - 85 years Health Status: unhealthy Age Group: 18 - 85 years Sex: M+F Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf	Disc. AE: Syncope... AEs leading to discontinuation/dose reduction: Syncope (1 patient) Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf
80 mg 1 times / day steady, oral Recommended Dose: 80 mg, 1 times / day Route: oral Route: steady Dose: 80 mg, 1 times / day Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf	unhealthy, 18 - 85 years Health Status: unhealthy Age Group: 18 - 85 years Sex: M+F Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf	Disc. AE: Syncope, Cardiac failure... AEs leading to discontinuation/dose reduction: Syncope (1 patient) Cardiac failure (1 patient) Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf
40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf	unhealthy, 26 - 84 years Health Status: unhealthy Age Group: 26 - 84 years Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf	Other AEs: Somnolence, Anticholinergic syndrome... Other AEs: Somnolence (10.9%) Anticholinergic syndrome (5.4%) Balance disorder (4.1%) Headache (3.4%) Akathisia (2.7%) Vomiting (2.6%) Nausea (2.3%) Arthralgia (2.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf
80 mg 1 times / day steady, oral Recommended Dose: 80 mg, 1 times / day Route: oral Route: steady Dose: 80 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf	unhealthy, 26 - 84 years Health Status: unhealthy Age Group: 26 - 84 years Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf

AEs

AE	Significance	Dose	Population
Syncope	1 patient Disc. AE	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf	unhealthy, 18 - 85 years Health Status: unhealthy Age Group: 18 - 85 years Sex: M+F Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf
Cardiac failure	1 patient Disc. AE	80 mg 1 times / day steady, oral Recommended Dose: 80 mg, 1 times / day Route: oral Route: steady Dose: 80 mg, 1 times / day Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf	unhealthy, 18 - 85 years Health Status: unhealthy Age Group: 18 - 85 years Sex: M+F Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf
Syncope	1 patient Disc. AE	80 mg 1 times / day steady, oral Recommended Dose: 80 mg, 1 times / day Route: oral Route: steady Dose: 80 mg, 1 times / day Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf	unhealthy, 18 - 85 years Health Status: unhealthy Age Group: 18 - 85 years Sex: M+F Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878201/pdf/40264_2017_Article_623.pdf
Somnolence	10.9%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf	unhealthy, 26 - 84 years Health Status: unhealthy Age Group: 26 - 84 years Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf
Arthralgia	2.3%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf	unhealthy, 26 - 84 years Health Status: unhealthy Age Group: 26 - 84 years Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf
Nausea	2.3%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf	unhealthy, 26 - 84 years Health Status: unhealthy Age Group: 26 - 84 years Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf
Vomiting	2.6%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf	unhealthy, 26 - 84 years Health Status: unhealthy Age Group: 26 - 84 years Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf
Akathisia	2.7%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf	unhealthy, 26 - 84 years Health Status: unhealthy Age Group: 26 - 84 years Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf
Headache	3.4%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf	unhealthy, 26 - 84 years Health Status: unhealthy Age Group: 26 - 84 years Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf
Balance disorder	4.1%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf	unhealthy, 26 - 84 years Health Status: unhealthy Age Group: 26 - 84 years Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf
Anticholinergic syndrome	5.4%	40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf	unhealthy, 26 - 84 years Health Status: unhealthy Age Group: 26 - 84 years Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209241lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 910 OAT1 725 OAT3 747 OCT2 779 OATP1B1 1079 OATP1B3 961 CYP1A2 2153 CYP2B6 926 CYP2C8 1057 CYP2C19 2057 CYP2E1 1060 CYP3A4/5 296	esterase 74 UGT 219 P-gp 2052	CYP1A2 832 CYP2B6 669 CYP3A4/5 133

Drug as perpetrator

Target	Modality	Activity
BCRP 985	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP1A2 2333	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP2B6 1160	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP3A4/5 357	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP3A4/5 357	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
OAT1 730	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
OAT3 749	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
OATP1B1 1095	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
OATP1B3 970	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
OCT2 782	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=14 Page: 14.0	unlikely
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Orig1s000PharmR.pdf#page=32 Page: 32.0	yes [IC50 14.2 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Orig1s000PharmR.pdf#page=25 Page: 25.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=7 Page: 7;30	yes
UGT 219	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Orig1s000PharmR.pdf#page=30 Page: 30.0	yes
esterase 74	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Orig1s000PharmR.pdf#page=30 Page: 30.0	yes
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=22 Page: 22;30	yes	yes (co-administration study) Comment: administered with ketoconazole: (similar PK parameters with parent drug) approximately 1.5-fold and 2-fold increase in the Cmax and AUC0-inf, respectively; administered with rifampin: about 50% decrease in Cmax and 80% decrease in AUC0-inf Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Oirg1s000ClinPharmR.pdf#page=22 Page: 22;30

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Orig1s000PharmR.pdf#page=24 Page: 24.0

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA004RNP	https://www.aablocks.com/goods/Goods/detail?id=AA004RNP
Acorn PharmaTech	ACN-052011	http://www.acornpharmatech.com/
Ambinter	Amb19131894	http://www.ambinter.com/reference/19131894
ApexBio Technology	B1268	http://www.apexbt.com/nbi-98782.html
BioCrick	BCC4277	http://www.biocrick.com/NBI-98782-BCC4277.html
Boerchem	BC686671	http://www.boerchem.com/?product_40360.html
Chem Scene	CS-1899	http://www.chemscene.com/85081-18-1.html
ChemMol	30116008	http://www.chemmol.com/chemmol/30116008.html
ChemMol	44011746	http://www.chemmol.com/chemmol/44011746.html
ChemMol	49422526	http://www.chemmol.com/chemmol/49422526.html
ChemMol	99084375	http://www.chemmol.com/chemmol/99084375.html
Chemspace	CSSB00102513434	https://chem-space.com/CSSB00102513434
MedChem Express	HY-15793	https://www.medchemexpress.com/nbi-98782.html
MuseChem	I005104	https://www.musechem.com/product/I005104.html
OChem	21713	http://www.ocheminc.com/index.php?act=psearch&pid=081D181
Smolecule	S649206	https://www.smolecule.com/products/s649206
Synblock Inc	SB18190	http://www.synblock.com/product/85081-18-1.html
THE BioTek	bt-352749	https://www.thebiotek.com/product/others/bt-352749
Yuhao Chemical	YH89670	http://www.chemyuhao.com/85081-18-1.html

PubMed

Title	Date	PubMed
Lessons from 11C-dihydrotetrabenazine imaging in a xenograft mouse model of rat insulinoma: is PET imaging of pancreatic beta cell mass feasible?	2017-12	25881691
Differences in Dihydrotetrabenazine Isomer Concentrations Following Administration of Tetrabenazine and Valbenazine.	2017-09	28776237
Early synaptic dysfunction induced by α-synuclein in a rat model of Parkinson's disease.	2017-07-25	28743955
Pharmacologic Characterization of Valbenazine (NBI-98854) and Its Metabolites.	2017-06	28404690
A ring-closing metathesis-based approach to the synthesis of (+)-tetrabenazine.	2012-07-20	22742980

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 `Wed Apr 02 09:53:04 GMT 2025` Edited by `admin` on `Wed Apr 02 09:53:04 GMT 2025`
Record UNII	OHZ3DQX6Q3
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

?-Dihydrotetrabenazine

Common Name

English

SD-946

Preferred Name

English

REL-(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

.ALPHA.-HTBN

Common Name

English

TRANS (2,3)-DIHYDROTETRABENAZINE

Common Name

English

TETRABENAZINE METABOLITE M6

Common Name

English

2H-BENZO(A)QUINOLIZIN-2-OL, 1,3,4,6,7,11B-HEXAHYDRO-9,10-DIMETHOXY-3-(2-METHYLPROPYL)-, (2R,3R,11BR)-REL-

Systematic Name

English

(±)-.ALPHA.-HTBN

Common Name

English

Code System Code Type Description

CAS

171598-74-6

Created by admin on Wed Apr 02 09:53:04 GMT 2025 , Edited by admin on Wed Apr 02 09:53:04 GMT 2025

PRIMARY

FDA UNII

OHZ3DQX6Q3

Created by admin on Wed Apr 02 09:53:04 GMT 2025 , Edited by admin on Wed Apr 02 09:53:04 GMT 2025

PRIMARY

Related Record Type Details


					ZB8VJ0T3SK

(-)-.ALPHA.-DIHYDROTETRABENAZINE

ENANTIOMER -> RACEMATE

Amount:


					IFRYDMLSGE

(+)-?-Dihydrotetrabenazine

ENANTIOMER -> RACEMATE

Amount:

Related Record Type Details


					Z9O08YRN8O

TETRABENAZINE

PARENT -> METABOLITE ACTIVE

Amount:

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/9094204 | http://adisinsight.springer.com/drugs/800046946

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Launch Date

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9094204 | http://adisinsight.springer.com/drugs/800046946

C_max

T_1/2

F_unbound

Drug as perpetrator