| Size | Price | Stock | Qty |
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| 1mg |
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| Targets |
VMAT2, a 12-transmembrane domain protein localized on synaptic vesicles. NBI-98782 binds with high affinity to a site distinct from the substrate, blocking monoamine accumulation. This reduces the quantal size of transmitter release, particularly in dopaminergic pathways, without blocking postsynaptic receptors. The H3 antagonist activity may enhance wakefulness and cognitive function, potentially offsetting some sedation associated with VMAT2 inhibition.
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| ln Vitro |
In vitro, NBI-98782 inhibits [3H]dihydrotetrabenazine binding to VMAT2 with Ki 0.97 nM. In synaptosome preparations, it reduces dopamine uptake into vesicles with IC50 ~1 nM. It also displaces [3H]N-α-methylhistamine from H3 receptors with moderate affinity (Ki ~50 nM). At concentrations up to 100 nM, it shows no significant binding to other neurotransmitter transporters (DAT, NET, SERT) or receptors (D1, D2, 5-HT2A).
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| ln Vivo |
In vivo, NBI-98782, as the active form, mediates the pharmacological effects of tetrabenazine and valbenazine. In rodents, it depletes brain monoamine stores and reduces amphetamine-induced hyperlocomotion. Its duration of action is longer than that of tetrabenazine due to a longer half-life. In clinical settings, it is responsible for the therapeutic efficacy in reducing chorea and dyskinesia, with a low risk of extrapyramidal side effects compared to typical antipsychotics.
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| Enzyme Assay |
Cell-free VMAT2 binding assays use membranes from rat striatum or recombinant human VMAT2 expressed in HEK-293 cells. Incubate with [3H]dihydrotetrabenazine (2 nM) and varying NBI-98782 concentrations in 50 mM HEPES buffer (pH 7.4) with 150 mM NaCl and 1 mM EDTA. Nonspecific binding defined with 10 µM tetrabenazine. After 1 h at 25°C, filter and count. Ki calculated. For H3 receptor, use [3H]N-α-methylhistamine on human H3-expressing membranes.
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| Cell Assay |
For VMAT2 functional assay, prepare rat striatal synaptosomes and incubate with [3H]dopamine (0.1 µM) and varying NBI-98782 in the presence of ATP and Mg2+. After 10 min, filter and measure vesicular accumulation. For H3 functional assay, measure inhibition of forskolin-stimulated cAMP in CHO cells expressing H3 receptor. Cells are treated with compound and stimulated with histamine; cAMP is measured by HTRF.
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| Animal Protocol |
In vivo, NBI-98782 is typically administered intraperitoneally to mice at 1–5 mg/kg. Effects on motor activity are assessed in open field or rotarod tests. For depletion studies, animals are sacrificed 1–4 h after dosing, and striatal dopamine, norepinephrine, and serotonin levels are measured by HPLC-ECD. The compound can be used in models of Huntington's disease (e.g., R6/2 mice) to evaluate reduction in choreiform movements, measured by blinded video scoring.
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| ADME/Pharmacokinetics |
Molecular formula C19H29NO3, MW 319.44. Appearance: solid. Solubility: DMSO (≥10 mg/mL). Storage: powder at -20°C, protect from light. Purity >98%. For in vivo, dissolve in saline with 5% Tween-80. LogP ~3.2, plasma protein binding ~80%. Half-life in rats ~3 h. Metabolism primarily by CYP2D6 and glucuronidation.
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| Toxicity/Toxicokinetics |
In clinical use, the parent drugs are well-tolerated; common side effects include sedation, depression, and parkinsonism. NBI-98782 itself has similar profile. High doses may cause akathisia. No significant hepatotoxicity or cardiotoxicity. Contraindicated in patients with severe depression or hepatic impairment. Suicide risk requires monitoring.
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| References | |
| Additional Infomation |
(2R,3R,11bR)-9,10-dimethoxy-3-(2-methylpropyl)-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinoline-2-ol is a member of the isoquinoline class of compounds.
NBI-98782 is not a commercial drug but the active moiety. It is used in research to study VMAT2 function and as a reference standard for metabolite analysis. Valbenazine (Ingrezza) is FDA-approved for tardive dyskinesia; tetrabenazine (Xenazine) for Huntington's chorea. The H3 antagonist activity is a distinct feature that may offer advantages over other VMAT2 inhibitors. |
| Molecular Formula |
C₁₉H₂₉NO₃
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|---|---|
| Molecular Weight |
319.44
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| Exact Mass |
319.214
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| CAS # |
85081-18-1
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| Related CAS # |
Trans (2,3)-Dihydrotetrabenazine;171598-74-6
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| PubChem CID |
14580381
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| Appearance |
White to off-white solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
457.8±45.0 °C at 760 mmHg
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| Flash Point |
230.7±28.7 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.562
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| LogP |
3.17
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
23
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| Complexity |
389
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC(C)C[C@@H]1CN2CCC3=CC(=C(C=C3[C@H]2C[C@H]1O)OC)OC
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| InChi Key |
WEQLWGNDNRARGE-DJIMGWMZSA-N
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| 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/t14-,16-,17-/m1/s1
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| Chemical Name |
(2R,3R,11bR)-9,10-dimethoxy-3-(2-methylpropyl)-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizin-2-ol
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| Synonyms |
(+-α-DHTBZ; (+-α-Dihydrotetrabenazine; (+-DTBZ
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~33.33 mg/mL (~104.34 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.83 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1305 mL | 15.6524 mL | 31.3048 mL | |
| 5 mM | 0.6261 mL | 3.1305 mL | 6.2610 mL | |
| 10 mM | 0.3130 mL | 1.5652 mL | 3.1305 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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