Deutetrabenazine

Deutetrabenazine (trade name Austedo) is a vesicular monoamine transporter 2 inhibitor which is used for the treatment of chorea associated with Huntington's disease and tardive dyskinesia.

Deutetrabenazine
Clinical data
Trade namesAustedo
Other namesTetrabenazine D6; SD809; SD-809
AHFS/Drugs.comMonograph
MedlinePlusa617022
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Identifiers
IUPAC name
  • (3R,11bR)-3-(2-Methylpropyl)-9,10-bis(trideuteriomethoxy)-1,3,4,6,7,11b-hexahydrobenzo[a]quinolizin-2-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC19H21D6NO3
Molar mass323.462 g·mol−1

Chemically, deutetrabenazine is an isotopic isomer of tetrabenazine in which six hydrogen atoms have been replaced by deuterium atoms. The incorporation of deuterium slows the rate of drug metabolism, allowing less frequent dosing.[3][4]

Efficacy

A Lancet study published on 28 June 2017 carried out a review between 29 October 2014 and 19 August 2016 where 298 patients were randomly assigned to receive at least one of the following: one dose of placebo per day, one dose of deutetrabenazine 12 mg/day, one dose of deutetrabenazine 24 mg/day, or one dose of deutetrabenazine 36 mg/day. From baseline to week 12, the least-squares mean AIMS (Abnormal Involuntary Movement Scale) score improved by −3.3 points in the deutetrabenazine 36 mg/day group, −3.2 points in the 24 mg/day group, −2.1 points in the 12 mg/day group, and −1.4 points in the placebo group. Deutetrabenazine 24 mg/day and 36 mg/day provided a significant reduction in tardive dyskinesia, with favourable safety and tolerability. These findings suggest that dosing regimens could be individualized and tailored for patients on the basis of dyskinesia control and tolerability.[5]

Pharmacology

Pharmacodynamics

Deutetrabenazine acts as a monoamine-depleting agent.

History

Teva Pharmaceuticals received approval from the Food and Drug Administration to market deutetrabenazine in early 2017, along with five years of orphan drug exclusivity for the treatment of chorea associated with Huntington's disease. It was the first deuterated drug to receive FDA approval.[6][7][8]

References
  1. "Austedo". Therapeutic Goods Administration (TGA). 9 June 2021. Archived from the original on 6 September 2021. Retrieved 6 September 2021.
  2. "AusPAR: Deutetrabenazine". Therapeutic Goods Administration (TGA). 27 May 2022. Archived from the original on 27 May 2022. Retrieved 13 June 2022.
  3. Citrome L (April 2016). "Breakthrough Drugs for the Interface Between Psychiatry and Neurology". International Journal of Clinical Practice. 70 (4): 298–9. doi:10.1111/ijcp.12805. PMID 27028671. Archived from the original on 21 August 2020. Retrieved 4 April 2017.
  4. Coppen EM, Roos RA (January 2017). "Current Pharmacological Approaches to Reduce Chorea in Huntington's Disease". Drugs. 77 (1): 29–46. doi:10.1007/s40265-016-0670-4. PMC 5216093. PMID 27988871.
  5. Anderson, Karen E; Stamler, David; Davis, Mat D; Factor, Stewart A; Hauser, Robert A; Isojärvi, Jouko; Fredrik L, Jarskog; Jimenez-Shahed, Joohi; Kumar, Rajeev; McEvoy, Joseph P; Ochudlo, Stanislaw; Ondo, William G; Fernandez, Hubert H (28 June 2017). "Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia (AIM-TD): a double-blind, randomised, placebo-controlled, phase 3 trial". The Lancet. 4 (8): 595–604. doi:10.1016/S2215-0366(17)30236-5. PMID 28668671. Archived from the original on 28 August 2021. Retrieved 4 February 2018.
  6. "FDA Approves Drug for Huntington's Disease". 3 April 2017. Archived from the original on 23 January 2019. Retrieved 4 April 2017.
  7. Schmidt, C (7 June 2017). "First deuterated drug approved". Nature Biotechnology. 35 (6): 493–494. doi:10.1038/nbt0617-493. PMID 28591114. S2CID 205269152.
  8. "FDA Determines that Deuterated Compounds are NCEs and Different Orphan Drugs Versus Non-deuterated Versions". FDA Law Blog. 16 July 2017. Archived from the original on 7 November 2017. Retrieved 5 November 2017.

Further reading
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