Reversible VMAT2 inhibitor
Vesicular monoamine transporter 2 inhibitor
- ↓ vesicular monoamine packaging
- Cytoplasmic monoamines are degraded → ↓ chorea and tardive dyskinesia
- Depression, parkinsonism and akathisia track the depletion; reversible on withdrawal
Reversible VMAT2 inhibitor (1/3)
- Blocks vesicular monoamine transporter-2
- ➔ prevents vesicular packaging of DA, NE, 5-HT, histamine
- ➔ therapeutic emphasis = DA ◇ but all monoamines depleted
- Indications
- ➔ tardive dyskinesia (TD)
- ➔ Huntington’s chorea
- Vesicular monoamine depletion (“dopamine depleters”)
- ➔ deutetrabenazine
Reversible VMAT2 inhibitor (2/3)
- Mechanistic rationale in TD
- ➔ TD = hypersensitized D2 receptors + phasic DA surges
- ➔ VMAT2 inhibition → ↓ vesicular DA stores
- ➔ each burst → smaller DA release
- Adverse effects
- ➔ depression (5-HT depletion)
- ➔ parkinsonism (↓ DA)
- ➔ akathisia (uncommon)
- Potential antipsychotic-like effects
- ➔ via reduced presynaptic DA release
- ➔ not primary clinical role
Reversible VMAT2 inhibitor (3/3)
- ➔ nonselective VMAT1 + VMAT2
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.
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