Synonym
Dihydrotetrabenazine, DTBZ, trans-(2,3)-Dihydro Tetrabenazine; b-Dihydrotetrabenazine
IUPAC/Chemical Name
1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2H-benzo[a]quinolizin-2-ol
InChi Key
WEQLWGNDNRARGE-UHFFFAOYSA-N
InChi Code
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
SMILES Code
OC1C(CC(C)C)CN2C(C(C=C(OC)C(OC)=C3)=C3CC2)C1
Purity
>98% (mixture of isomers)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Dihydrotetrabenazine (racemic) is an active metabolite of the vesicular monoamine transporter 2 (VMAT2) inhibitor tetrabenazine that is generated by hepatic carbonyl reductases.
In vitro activity:
The result of VMAT2 binding assay revealed that (+)-1 (Ki=4.47 nM) was 8000-fold more potent than (-)-1 (Ki=36,400 nM). Among all eight DHTBZ (dihydrotetrabenazines) stereoisomers, (2R,3R,11bR)-DHTBZ ((+)-2: Ki=3.96 nM) showed the greatest affinity for VMAT2.
Reference: Eur J Med Chem. 2011 May;46(5):1841-8. https://pubmed.ncbi.nlm.nih.gov/21396745/
In vivo activity:
The results (Figure 3A) indicated that in the dose range of 0.16–10.4 μmol/kg, (+)-13e (9-trifluoroethoxy-dihydrotetrabenazine) inhibited the locomotor activity of rats in a dose-dependent manner (RR = 18.6–98.9%).
Reference: Front Pharmacol. 2021 Dec 7;12:770377. https://pubmed.ncbi.nlm.nih.gov/34950030/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
319.45
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Yao Z, Wei X, Wu X, Katz JL, Kopajtic T, Greig NH, Sun H. Preparation and evaluation of tetrabenazine enantiomers and all eight stereoisomers of dihydrotetrabenazine as VMAT2 inhibitors. Eur J Med Chem. 2011 May;46(5):1841-8. doi: 10.1016/j.ejmech.2011.02.046. Epub 2011 Feb 23. PMID: 21396745; PMCID: PMC6191844.
2. Wang W, Du G, Lin S, Liu J, Yang H, Yu D, Ye L, Zou F, Wang H, Zhang R, Tian J. (+)-9-Trifluoroethoxy-α-Dihydrotetrabenazine as a Highly Potent Vesicular Monoamine Transporter 2 Inhibitor for Tardive Dyskinesia. Front Pharmacol. 2021 Dec 7;12:770377. doi: 10.3389/fphar.2021.770377. PMID: 34950030; PMCID: PMC8689140.
In vitro protocol:
1. Yao Z, Wei X, Wu X, Katz JL, Kopajtic T, Greig NH, Sun H. Preparation and evaluation of tetrabenazine enantiomers and all eight stereoisomers of dihydrotetrabenazine as VMAT2 inhibitors. Eur J Med Chem. 2011 May;46(5):1841-8. doi: 10.1016/j.ejmech.2011.02.046. Epub 2011 Feb 23. PMID: 21396745; PMCID: PMC6191844.
In vivo protocol:
1. Wang W, Du G, Lin S, Liu J, Yang H, Yu D, Ye L, Zou F, Wang H, Zhang R, Tian J. (+)-9-Trifluoroethoxy-α-Dihydrotetrabenazine as a Highly Potent Vesicular Monoamine Transporter 2 Inhibitor for Tardive Dyskinesia. Front Pharmacol. 2021 Dec 7;12:770377. doi: 10.3389/fphar.2021.770377. PMID: 34950030; PMCID: PMC8689140.
1. Chen, J.J., Ondo, W.G., Dashtipour, K., et al. Tetrabenazine for the treatment of hyperkinetic movement disorders: A review of the literature. Clin. Ther. 34(7), 1487-1504 (2012).
2. Scherman, D. Dihydrotetrabenazine binding and monoamine uptake in mouse brain regions. J. Neurochem. 47(2), 331-339 (1986).
3. Scherman, D., Raisman, R., Ploska, A., et al. [3H]dihydrotetrabenazine, a new in vitro monoaminergic probe for human brain. J. Neurochem. 50(4), 1131-1136 (1988).
4. Yao, Z., Wei, X., Wu, X., et al. Preparation and evaluation of tetrabenazine enantiomers and all eight stereoisomers of dihydrotetrabenazine as VMAT2 inhibitors. Eur. J. Med. Chem. 46(5), 1841-1848 (2011).
