Overview
Deutetrabenazine is a novel, highly selective vesicular monoamine transporter 2 (VMAT2) inhibitor indicated for the management of chorea associated with Huntington’s disease. It is a hexahydro-dimethoxybenzoquinolizine derivative and a deuterated Tetrabenazine . The presence of deuterium in deutetrabenazine increases the half-lives of the active metabolite and prolongs their pharmacological activity by attenuating CYP2D6 metabolism of the compound . This allows less frequent dosing and a lower daily dose with improvement in tolerability . Decreased plasma fluctuations of deutetrabenazine due to attenuated metabolism may explain a lower incidence of adverse reactions associated with deutetrabenazine . Deutetrabenazine is a racemic mixture containing RR-Deutetrabenazine and SS-Deutetrabenazine . Huntington's disease (HD) is a hereditary, progressive neurodegenerative disorder characterized by motor dysfunction, cognitive decline, and neuropsychiatric disturbances that interfere with daily functioning and significantly reduce the quality of life. The most prominent physical symptom of HD that may increase the risk of injury is chorea, which is an involuntary, sudden movement that can affect any muscle and flow randomly across body regions . Psychomotor symptoms of HD, such as chorea, are related to hyperactive dopaminergic neurotransmission . Deutetrabenazine depletes the levels of presynaptic dopamine by blocking VMAT2, which is responsible for the uptake of dopamine into synaptic vesicles in monoaminergic neurons and exocytotic release . As with other agents for the treatment of neurodegenerative diseases, deutetrabenazine is a drug to alleviate the motor symptoms of HD and is not proposed to halt the progression of the disease . In clinical trials of patients with HD, 12 weeks of treatment of deutetrabenazine resulted in overall improvement in mean total maximal chorea scores and motor signs than placebo . It was approved by FDA in April 2017 and is marketed under the trade name Austedo as oral tablets.
Indication
Deutetrabenazine is indicated in adults patients for the treatment of tardive dyskinesia and for chorea associated with Huntington's disease.
Associated Conditions
- Chorea
- Tardive Dyskinesia (TD)
Research Report
Deutetrabenazine (Austedo®): A Comprehensive Pharmacological and Clinical Monograph
Executive Summary
Deutetrabenazine is a highly selective, reversible inhibitor of the vesicular monoamine transporter 2 (VMAT2) indicated for the management of hyperkinetic movement disorders, specifically chorea associated with Huntington's disease and tardive dyskinesia in adults. Marketed under the brand names Austedo® and Austedo XR®, its development marks a significant milestone in medicinal chemistry as the first deuterated drug to receive approval from the U.S. Food and Drug Administration (FDA). Its mechanism of action, shared with its non-deuterated predecessor tetrabenazine, involves the depletion of presynaptic monoamines such as dopamine, thereby reducing the excessive dopaminergic signaling implicated in these conditions.
The core innovation of deutetrabenazine lies in the strategic replacement of specific hydrogen atoms with deuterium, a stable isotope of hydrogen. This molecular modification leverages the kinetic isotope effect to create a stronger carbon-deuterium bond, which attenuates the rate of metabolism by the cytochrome P450 2D6 (CYP2D6) enzyme system. This rational design confers a superior pharmacokinetic profile characterized by a longer half-life of its active metabolites, more stable plasma concentrations, and reduced peak-to-trough variability.
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
---|---|---|---|---|---|
2021/01/19 | Phase 2 | Recruiting | |||
2020/03/10 | Phase 1 | Terminated | |||
2019/12/16 | Phase 3 | Terminated | |||
2019/11/21 | Phase 1 | Active, not recruiting | |||
2019/08/28 | Phase 1 | Recruiting | Second Affiliated Hospital, School of Medicine, Zhejiang University | ||
2019/01/23 | Phase 3 | Completed | |||
2018/06/27 | Phase 3 | Completed | |||
2018/06/25 | Phase 3 | Terminated | |||
2018/03/02 | Phase 2 | Completed | |||
2016/02/04 | Phase 1 | Completed |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
---|---|---|---|---|---|
Teva Neuroscience, Inc. | 68546-471 | ORAL | 12 mg in 1 1 | 10/9/2023 | |
Teva Neuroscience, Inc. | 68546-171 | ORAL | 9 mg in 1 1 | 10/9/2023 | |
Teva Neuroscience, Inc. | 68546-470 | ORAL | 6 mg in 1 1 | 10/9/2023 | |
Teva Neuroscience, Inc. | 68546-172 | ORAL | 12 mg in 1 1 | 10/9/2023 | |
Teva Neuroscience, Inc. | 68546-472 | ORAL | 24 mg in 1 1 | 10/9/2023 | |
Teva Neuroscience, Inc. | 68546-170 | ORAL | 6 mg in 1 1 | 10/9/2023 |
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
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No EMA approvals found for this drug. |
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
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No HSA approvals found for this drug. |
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
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No NMPA approvals found for this drug. |
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
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No PPB approvals found for this drug. |
TGA Drug Approvals
Approved Product | ARTG ID | Sponsor | Registration Type | Status | Registration Date |
---|---|---|---|---|---|
AUSTEDO deutetrabenazine 9 mg modified release tablet bottle | 330021 | Medicine | A | 6/2/2021 | |
AUSTEDO deutetrabenazine12 mg modified release tablet bottle | 330022 | Medicine | A | 6/2/2021 | |
AUSTEDO deutetrabenazine 6 mg modified release tablet bottle | 330023 | Medicine | A | 6/2/2021 |
Health Canada Drug Approvals
Approved Product | Company | DIN | Dosage Form | Strength | Market Date |
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No Health Canada approvals found for this drug. |
CIMA AEMPS Drug Approvals
Approved Product | Company | Registration Number | Pharmaceutical Form | Prescription Type | Status |
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No CIMA AEMPS (Spain) approvals found for this drug. |
Philippines FDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
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No Philippines FDA approvals found for this drug. |
Saudi SFDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
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No Saudi SFDA approvals found for this drug. |
Malaysia NPRA Drug Approvals
Approved Product | Company | Registration Number | Dosage Form | Strength | Approval Date |
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No Malaysia NPRA approvals found for this drug. |
UK EMC Drug Information
Medicine Name | MA Holder | MA Number | Pharmaceutical Form | Active Ingredient | Authorization Date |
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No UK EMC drug information found for this drug. |
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