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
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
(+)-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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4828 |
0.97 nM [Ki] | ||
Target ID: Q05940 Gene ID: 6571.0 Gene Symbol: SLC18A2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/30160230 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | INGREZZA Approved UseINGREZZA is indicated for the treatment of adults with tardive dyskinesia Launch Date2017 |
Cmax
Value | Dose | Co-administered | 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 |
|
39.4 ng/mL |
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 |
|
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 |
|
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 |
|
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 |
AUC
Value | Dose | Co-administered | 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 |
|
695 ng × h/mL |
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 |
|
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 |
|
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 |
|
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 |
T1/2
Value | Dose | Co-administered | 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 |
|
18.5 h |
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 |
|
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 |
|
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 |
|
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 |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
36% |
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: |
unhealthy, 18 - 85 years n = 110 Health Status: unhealthy Condition: schizophrenia or schizoaffective disorder, or mood disorder Age Group: 18 - 85 years Sex: M+F Population Size: 110 Sources: |
Disc. AE: Syncope... AEs leading to discontinuation/dose reduction: Syncope (1 patient) Sources: |
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: |
unhealthy, 18 - 85 years n = 112 Health Status: unhealthy Condition: schizophrenia or schizoaffective disorder, or mood disorder Age Group: 18 - 85 years Sex: M+F Population Size: 112 Sources: |
Disc. AE: Syncope, Cardiac failure... AEs leading to discontinuation/dose reduction: Syncope (1 patient) Sources: Cardiac failure (1 patient) |
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: Page: Table 1 |
unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: Page: Table 1 |
Other AEs: Somnolence, Anticholinergic syndrome... Other AEs: Somnolence (10.9%) Sources: Page: Table 1Anticholinergic syndrome (5.4%) Balance disorder (4.1%) Headache (3.4%) Akathisia (2.7%) Vomiting (2.6%) Nausea (2.3%) Arthralgia (2.3%) |
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: Page: 8.1 |
unhealthy, 26 - 84 years Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Sources: Page: 8.1 |
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: |
unhealthy, 18 - 85 years n = 110 Health Status: unhealthy Condition: schizophrenia or schizoaffective disorder, or mood disorder Age Group: 18 - 85 years Sex: M+F Population Size: 110 Sources: |
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: |
unhealthy, 18 - 85 years n = 112 Health Status: unhealthy Condition: schizophrenia or schizoaffective disorder, or mood disorder Age Group: 18 - 85 years Sex: M+F Population Size: 112 Sources: |
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: |
unhealthy, 18 - 85 years n = 112 Health Status: unhealthy Condition: schizophrenia or schizoaffective disorder, or mood disorder Age Group: 18 - 85 years Sex: M+F Population Size: 112 Sources: |
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: Page: Table 1 |
unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: Page: Table 1 |
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: Page: Table 1 |
unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: Page: Table 1 |
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: Page: Table 1 |
unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: Page: Table 1 |
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: Page: Table 1 |
unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: Page: Table 1 |
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: Page: Table 1 |
unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: Page: Table 1 |
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: Page: Table 1 |
unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: Page: Table 1 |
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: Page: Table 1 |
unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: Page: Table 1 |
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: Page: Table 1 |
unhealthy, 26 - 84 years n = 262 Health Status: unhealthy Condition: tardive dyskinesia Age Group: 26 - 84 years Sex: unknown Population Size: 262 Sources: Page: Table 1 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209241Orig1s000PharmR.pdf#page=24 Page: 24.0 |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT02844179
Single dose administration of (+)-alpha-Dihydrotetrabenazine (HTBZ), escalating dosage amounts 7.5 - 30 mg orally
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7589162
(+)-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).
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
607417
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FDA ORPHAN DRUG |
498715
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14580381
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DTXSID30561896
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300000044642
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IFRYDMLSGE
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85081-18-1
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PRODRUG (METABOLITE ACTIVE)
SUBSTANCE RECORD