Tetrabenazine API is a synthetic small-molecule vesicular monoamine transporter 2 (VMAT2) inhibitor belonging to the benzoquinolizine class. It reduces the storage and release of monoamines, particularly dopamine, from presynaptic nerve terminals. Tetrabenazine is the active pharmaceutical ingredient in XENAZINE, which received FDA approval in 2008 for the treatment of chorea associated with Huntington's disease.
Tetrabenazine has the molecular formula C19H27NO3 and molecular weight 317.43 g/mol. PubChem identifies CAS 58-46-8 as a principal CAS number for tetrabenazine and FDA GSRS lists the substance under the same chemical identity.
Tetrabenazine is also available as a USP Reference Standard, confirming its recognized role in pharmaceutical quality testing and analytical applications.
Tetrabenazine is chemically described as 9,10-dimethoxy-3-(2-methylpropyl)-1,3,4,6,7,11b-hexahydrobenzo[a]quinolizin-2-one. The molecule contains stereogenic centers, and its stereochemical composition is important because tetrabenazine is associated with multiple stereoisomeric forms. PubChem separately identifies individual tetrabenazine stereoisomers, including the (+)- and (-)-forms.
The commercially used pharmaceutical substance is commonly represented as tetrabenazine, while tetrabenazine hydrochloride is a separate chemical form with CAS 2105-47-7 and molecular weight approximately 353.9 g/mol. Therefore, the free tetrabenazine API and hydrochloride should not be treated as interchangeable substances in product data.
| Property | Value |
|---|---|
| Product Name | Tetrabenazine |
| CAS Number | 58-46-8 |
| Molecular Formula | C19H27NO3 |
| Molecular Weight | 317.43 g/mol |
| Chemical Class | Benzoquinolizine derivative |
| Pharmacological Class | VMAT2 inhibitor |
| Therapeutic Category | CNS / Movement Disorders |
| FDA UNII | Z9O08YRN8O |
| Appearance | White to light-yellow powder to crystal |
PubChem reports C19H27NO3 and molecular weight 317.4 g/mol, while TCI reports 317.43 g/mol and describes the material as a white to light-yellow powder to crystal.
Tetrabenazine inhibits vesicular monoamine transporter 2 (VMAT2). VMAT2 is responsible for transporting monoamines into synaptic vesicles. Inhibition reduces vesicular monoamine storage and consequently decreases dopamine availability for synaptic release.
The FDA identifies tetrabenazine as a VMAT2 inhibitor indicated for the treatment of chorea associated with Huntington's disease.
The principal FDA-approved pharmaceutical application of tetrabenazine is the treatment of chorea associated with Huntington's disease. FDA records show XENAZINE/tetrabenazine received U.S. marketing approval on August 15, 2008 for this indication.
Tetrabenazine has also been investigated and used in other hyperkinetic movement disorders in various jurisdictions and clinical settings. However, such uses should not be represented as FDA-approved indications unless supported by the applicable regulatory authorization.
Tetrabenazine has a recognized USP Reference Standard, and current analytical literature demonstrates the need for comprehensive control of related substances. A 2025 Journal of Pharmaceutical and Biomedical Analysis study developed GC-FID and HPLC-RID procedures covering 12 related substances, including aldehyde, ketone and quaternary ammonium impurities. The researchers established impurity limits of approximately 0.1% for the detected related substances in their analytical control program.
For API quality control, appropriate analytical characterization may include:
TCI currently specifies minimum 99.0 area% HPLC purity and minimum 99.0% nonaqueous titration purity for its analytical-grade tetrabenazine reference material. This is a commercial specification, not a universal pharmacopoeial API release limit.
Tetrabenazine is a synthetic small-molecule API manufactured through controlled chemical synthesis followed by purification and crystallization. Modern analytical work has emphasized controlling impurity transmission throughout the synthetic route, including impurities originating from starting materials and reaction intermediates.
A qualified Tetrabenazine API Manufacturer in India should maintain validated manufacturing and analytical processes capable of controlling chemical purity, stereochemical composition, residual solvents and process-related impurities.
Tetrabenazine is a solid crystalline material. PubChem reports experimental melting-point values around 126–129°C, while TCI specifies 124–130°C for its reference product.
Tetrabenazine has limited aqueous solubility that is strongly dependent on pH. A published formulation study reported approximately 850 mg/100 mL at pH 2, approximately 4 mg/100 mL at pH 3, and approximately 3 mg/100 mL from pH 4 through pH 12. These values are experimental physicochemical data and should not be confused with a pharmacopoeial release specification.
TCI specifies storage at 0–10°C, under inert gas, and identifies tetrabenazine as heat- and air-sensitive for its analytical product.
For pharmaceutical API, actual packaging and storage conditions should be based on the validated stability program and approved manufacturer/customer specification.
A professional Tetrabenazine API supply package may include:
A reliable Tetrabenazine API Manufacturer in India should provide consistent pharmaceutical-grade material supported by validated analytical methods, controlled manufacturing processes and complete batch documentation. Particular attention should be given to related substances and stereochemical purity because tetrabenazine contains stereogenic centers and modern analytical literature identifies numerous potential process-related impurities.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | NLT 99.0% |
| Individual Impurity | NMT 0.1% |
| Melting Point | 124–130°C (TCI specification) |
| Solubility | Approx. 3.0 mg/100 mL at pH 4–12; approx. 4.0 mg/100 mL at pH 3; approx. 850 mg/100 mL at pH 2 |