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. SLC18A2 is an integral membrane protein that transports monoamines—partic ...

inhibitor which is used for the treatment of

chorea Chorea (or choreia, occasionally) is an abnormal involuntary movement disorder, one of a group of neurological disorders called dyskinesias. The term ''chorea'' is derived from the grc, χορεία ("dance"; see choreia), as the quick movem ...

associated with

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an uns ...

and

tardive dyskinesia Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movemen ...

. 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 U.S. Food and Drug Administration approved the use of tetrabena ...

in which six hydrogen atoms have been replaced by

deuterium Deuterium (or hydrogen-2, symbol or deuterium, also known as heavy hydrogen) is one of two stable isotopes of hydrogen (the other being protium, or hydrogen-1). The nucleus of a deuterium atom, called a deuteron, contains one proton and one ...

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 Monoamine-depleting agents are a group of drugs which reversibly deplete one or more monoamine neurotransmitters. One mechanism by which these agents act is by inhibiting reuptake by the vesicular monoamine transporters, VMAT1 and VMAT2. Example ...

History

Teva Pharmaceuticals 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 respon ...

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.

References

External links