From the Guidelines
Deutetrabenazine is a vesicular monoamine transporter 2 (VMAT2) inhibitor, which is a drug class that regulates the levels of dopamine in the brain. This classification is based on the mechanism of action of deutetrabenazine, which involves blocking VMAT2 to reduce excessive, involuntary movements associated with conditions like tardive dyskinesia and chorea in Huntington's disease 1. The drug works by inhibiting the transport of monoamines, such as dopamine, into synaptic vesicles, thereby decreasing the amount of dopamine available for release.
- Key characteristics of deutetrabenazine include:
- Deuterated form of tetrabenazine, allowing for more stable blood levels and less frequent dosing
- Typically started at a low dose and gradually increased to minimize side effects
- Common side effects include sedation, depression, and parkinsonism
- Requires long-term treatment for chronic movement disorders
- Patients should be monitored for depression and suicidal thoughts, as VMAT2 inhibitors can potentially worsen these conditions in susceptible individuals. Although the provided study 1 focuses on in vivo imaging of beta cells with radiotracers, it mentions the high-affinity ligand dihydrotetrabenazine (DTBZ) and its target, VMAT2, which is also relevant to deutetrabenazine's mechanism of action.
From the FDA Drug Label
The precise mechanism by which deutetrabenazine exerts its effects in the treatment of tardive dyskinesia and chorea in patients with Huntington’s disease is unknown but is believed to be related to its effect as a reversible depletor of monoamines (such as dopamine, serotonin, norepinephrine, and histamine) from nerve terminals The major circulating metabolites (α-dihydrotetrabenazine [HTBZ] and β-HTBZ) of deutetrabenazine, are reversible inhibitors of VMAT2, resulting in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores. AUSTEDO XR extended-release tablets and AUSTEDO tablets are formulated with deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor for oral administration.
The drug class of deutetrabenazine is a vesicular monoamine transporter 2 (VMAT2) inhibitor 2.
From the Research
Deutetrabenazine Drug Class
- Deutetrabenazine is a vesicular monoamine transporter 2 (VMAT2) inhibitor 3, 4, 5, 6, 7
- It is structurally similar to tetrabenazine, but with deuterium modifications that improve its pharmacokinetic profile 3
- Deutetrabenazine is approved by the US Food and Drug Administration (FDA) for the treatment of Huntington's disease-associated chorea and tardive dyskinesia 3, 6, 7
- As a VMAT2 inhibitor, deutetrabenazine depletes monoamines at presynaptic nerve terminals, which helps to reduce the symptoms of hyperkinetic movement disorders such as tardive dyskinesia and chorea associated with Huntington's disease 4, 5, 6
Mechanism of Action
- Deutetrabenazine works by inhibiting the vesicular monoamine transporter 2 (VMAT2), which is responsible for transporting monoamines such as dopamine, serotonin, and norepinephrine into synaptic vesicles 3, 4, 5, 6
- By inhibiting VMAT2, deutetrabenazine reduces the amount of monoamines available for release into the synaptic cleft, which helps to reduce the symptoms of hyperkinetic movement disorders 3, 4, 5, 6