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Pharmacology · VMAT2 inhibitors

Deutetrabenazine !

A deuterated form of tetrabenazine whose active metabolites last longer. Treats Huntington chorea and tardive dyskinesia.

Updated 2026-11-01

  • Class: VMAT2 inhibitors
  • Transporter: Vesicular monoamine transporter 2 (VMAT2)
  • ATC code: N07XX16

The figure shows tetrabenazine in human VMAT2; deutetrabenazine is the same molecule with some hydrogens replaced by deuterium and binds the same site.

Target in 3D: Vesicular monoamine transporter 2 (VMAT2). PDB structure 8JTA (RCSB PDB, public domain). View the structure at RCSB PDB

Mechanism of action

Deutetrabenazine is tetrabenazine with deuterium in place of some hydrogen atoms. The stronger carbon-deuterium bonds slow its metabolism (the kinetic isotope effect), so its active metabolites, which inhibit VMAT2, have longer half-lives. Dopamine stores are depleted and hyperkinetic movements decrease.

  1. Deuterium slows the breakdown of the active metabolites
  2. Metabolites block VMAT2 for longer
  3. Striatal dopamine release falls
  4. Chorea and tardive movements decrease

Pharmacokinetics

Metabolism
Active deuterated metabolites with longer half-lives than those of tetrabenazine; CYP2D6 involved

Indications

Adverse effects

Common

  • Tiredness and somnolence
  • Diarrhoea or constipation, dry mouth
  • Insomnia
  • Nasal congestion and sore throat

Contraindications

  • Liver disease
  • MAO inhibitors (and within two weeks of stopping them)
  • Tetrabenazine, valbenazine or reserpine
  • Suicidal or untreated depressed patients with Huntington disease

Key interactions

Strong CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine)
Higher exposure; dose is limited
QT-prolonging drugs
Additive QT risk
Alcohol and sedatives
More drowsiness

What is monitored

  • Mood and suicidal thoughts
  • Parkinsonism, gait and falls
  • ECG and potassium and magnesium when QT risk exists

Administration and safety

  • Tablets are swallowed whole, not split, chewed or crushed
  • Immediate-release and extended-release tablets are different products
  • Increased gradually, at most weekly

Nursing care

  • Screen for depression and suicidal thoughts and involve the family
  • Assess gait and fall risk
  • Warn about drowsiness and alcohol

Pregnancy and breastfeeding

Human data are lacking; pregnancy during treatment is discussed with the specialist.

Test yourself

Think of the answer, then tap the question to see it.

What does deuterium change in deutetrabenazine?

Stronger carbon-deuterium bonds slow metabolism, so the active VMAT2-inhibiting metabolites last longer.

Which two movement disorders is deutetrabenazine used for?

Chorea of Huntington disease and tardive dyskinesia.

Which psychiatric warning applies in Huntington disease?

Increased risk of depression and suicidal thoughts.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Deutetrabenazine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2024); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 21 (McGraw Hill, 2023); Farmacología básica y clínica (Katzung), 16.ª ed., cap. 28 (McGraw Hill, 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.