Reversible VMAT2 inhibitor
Vesicular monoamine transporter 2 inhibitor
- ↓ vesicular monoamine packaging
- prevents vesicular packaging of DA, NE, 5-HT, histamine
- therapeutic emphasis = DA ◇ but all monoamines depleted
- Vesicular monoamine depletion (“dopamine depleters”)
- deutetrabenazine
- nonselective VMAT1 + VMAT2
- Cytoplasmic monoamines are degraded → ↓ chorea and tardive dyskinesia
- Huntington’s chorea
- Mechanistic rationale in TD
- TD = hypersensitized D2 receptors + phasic DA surges
- VMAT2 inhibition → ↓ vesicular DA stores
- each burst → smaller DA release
- Depression, parkinsonism and akathisia track the depletion; reversible on withdrawal
- depression (5-HT depletion)
- parkinsonism (↓ DA)
- akathisia (uncommon)
- Potential antipsychotic-like effects
- via reduced presynaptic DA release
- not primary clinical role
Drugs with this mechanism (5)
- Deutetrabenazine XR — Once-daily extended-release deutetrabenazine for Huntington chorea and tardive dyskinesia; same total daily dose as twice-daily AUSTEDO.
- Deutetrabenazine — Deuterated VMAT2 inhibitor with steadier levels than tetrabenazine.
- [+]-α-HTBZ — Valbenazine's active metabolite; the VMAT2 inhibition the drug depends on.
- Tetrabenazine — VMAT2 inhibitor for Huntington chorea; depression and parkinsonism limit use.
- Valbenazine — Once-daily VMAT2 inhibitor for tardive dyskinesia.
Self-check
- Are VMAT2 inhibitors’ effects limited to dopamine?
No; all monoamines are depleted. - Are the listed depletion effects reversible on withdrawal?
Yes.
All mechanisms · Open VMAT2 inhibitor (reversible) in the interactive console ↗