Deutetrabenazine (trade name Austedo) is a

vesicular monoamine transporter 2 The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the ''SLC18A2'' gene. VMAT2 is an integral membrane protein that transports monoamines—particul ...

inhibitor which is used for the treatment of

chorea Chorea, or (rarely) choreia, () is an abnormal involuntary movement disorder, characterized by quick movements of the hands or feet. It is one of a group of neurological disorders called dyskinesias. The term ''chorea'' is derived , as the move ...

associated with

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is an incurable neurodegenerative disease that is mostly Genetic disorder#Autosomal dominant, inherited. It typically presents as a triad of progressive psychiatric, cognitive, and ...

and

tardive dyskinesia Tardive dyskinesia (TD) is an iatrogenic disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips, which occurs following treatment with medication. Additional mo ...

. Chemically, deutetrabenazine is an isotopic isomer of

tetrabenazine Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorders. It is sold under the brand names Nitoman and Xenazine among others. On August 15, 2008, the US Food and Drug Administration (FDA) approved the use of tet ...

in which six hydrogen atoms have been replaced by

deuterium Deuterium (hydrogen-2, symbol H or D, also known as heavy hydrogen) is one of two stable isotopes of hydrogen; the other is protium, or hydrogen-1, H. The deuterium nucleus (deuteron) contains one proton and one neutron, whereas the far more c ...

atoms. The incorporation of deuterium slows the rate of

drug metabolism Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set o ...

, allowing less frequent dosing.

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.

Pharmacology

Pharmacodynamics

Deutetrabenazine acts as a monoamine-depleting agent.

History

Teva Pharmaceuticals Teva Pharmaceutical Industries Ltd. (also known as Teva Pharmaceuticals) is an Israeli multinational Pharmaceutical industry, pharmaceutical company. Teva specializes primarily in generic drugs, but other business interests include branded-drug ...

received approval from the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

to market deutetrabenazine in early 2017, along with five years of

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

exclusivity for the treatment of chorea associated with Huntington's disease. It was the first

deuterated drug A deuterated drug is a small molecule medicinal product in which one or more of the hydrogen atoms in the drug molecule have been replaced by its heavier stable isotope deuterium. Because of the kinetic isotope effect, deuterium-containing drugs m ...

to receive FDA approval.

References

External links

* {{Portal bar , Medicine Antidyskinetic agents Deuterated compounds Huntington's disease Monoamine-depleting agents Norsalsolinol ethers VMAT inhibitors