Tetrabenazine

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Cat Number

API0231609

CAS Number

58-46-8

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Product Detail Description Scientific Support Customer Q&A

CAS Number

58-46-8

EINECS

200-383-6

Storage

Store at room temperature

Synonyms

Nitoman; Xenazine; Tetrabenazina; Tetrabenazinum

Molecular Formula

C19H27NO3

Molecular Weight

317.4

Smiles

CC(C)CC1CN2CCC3=CC(=C(C=C3C2CC1=O)OC)OC

Appearance

White to off-white solid

Melting Point

125-130℃

Boiling Point

448.9±45.0℃ (Predicted)

Relative Density

1.12±0.1 (Predicted)

General Description

Tetrabenazine is a reversible, selective inhibitor of vesicular monoamine transporter 2 (VMAT2), approved for the treatment of chorea associated with Huntington's disease. It was the first drug specifically indicated for Huntington-related movement disorders. The compound is a benzoquinolizine derivative unrelated to typical neuroleptics.

Mechanism of Action

Tetrabenazine binds to VMAT2 on synaptic vesicles of monoaminergic neurons, blocking the uptake of dopamine, serotonin, norepinephrine, and histamine into vesicles. This leads to depletion of monoamine stores in the presynaptic terminal, particularly dopamine, thereby reducing overactive dopaminergic signaling in the basal ganglia. Unlike antipsychotics, it does not block postsynaptic dopamine receptors. The drug has no significant affinity for D2 receptors.

Application

Tetrabenazine is indicated for the management of chorea (involuntary, jerky movements) in Huntington's disease, improving functional abilities and quality of life. It is also used off-label for other hyperkinetic movement disorders such as tardive dyskinesia, Tourette syndrome, and hemiballismus.

A retrospective analysis of 108 patients treated with tetrabenazine for Huntington disease, vascular chorea, tics, dystonia, tardive oromandibular dyskinesia, and other tardive syndromes found an overall clinically meaningful response rate of 87% sustained over 40 months. Response was highest in Huntington disease (100%) and lowest in tic disorders (62.5%) and oromandibular dyskinesia (77.1%). Adverse events occurred in 40–60% of patients; Parkinsonism (51.8%) and psychiatric disturbances (25%) predominated. Somnolence emerged early (median 3 months), while Parkinsonism appeared later during maintenance. The authors conclude tetrabenazine is effective and relatively well tolerated, though adverse event profiles differ by disorder and age.

Fig. 1 Tetrabenazine effectiveness results. (Miguel R, et al., 2017)

References

Miguel R, et al. Tetrabenazine in treatment of hyperkinetic movement disorders: an observational study. Ther Adv Neurol Disord. 2017;10(2):81-90.

Does Tetrabenazine require protection from light during storage?

Yes, it is photosensitive. Prolonged exposure to light can cause photodegradation and formation of the dihydrotetrabenazine impurity. Store in light-resistant containers.

What is the recommended storage temperature for Tetrabenazine?

Store at controlled room temperature (15-25°C). Avoid temperatures above 30°C, which can accelerate oxidative degradation of the benzoquinolizine ring.

Is Tetrabenazine hygroscopic, and how is this managed?

It exhibits low hygroscopicity. However, in high-humidity environments, storage in tightly sealed containers with desiccant is recommended to prevent caking.

How is the impurity dihydrotetrabenazine (a reduced form) monitored during stability?

This degradation product is specifically quantified using a stability-indicating HPLC method with electrochemical or UV detection, ensuring it remains within ICH limits.