Target: VMAT2
Status: Approved (TD), PD (emerging)
Mechanism: VMAT2 inhibition
The vesicular monoamine transporter 2 (VMAT2, encoded by SLC18A2) packages dopamine and other monoamines into synaptic vesicles for storage and release. VMAT2 modulators reduce available synaptic dopamine, making them useful for hyperkinetic movement disorders, with emerging applications in Parkinson's disease.
VMAT2 is essential for monoamine neurotransmission:
- Packages dopamine into synaptic vesicles
- Protects monoamines from enzymatic degradation
- Regulates quantal dopamine release
| Attribute |
Details |
| Company |
Neurocrine Biosciences |
| Product |
Ingrezza |
| Indication |
Tardive Dyskinesia (approved), HD (Phase 3) |
| Mechanism |
Selective VMAT2 inhibitor |
| Status |
Approved 2017 |
Valbenazine was the first FDA-approved drug specifically for tardive dyskinesia. It provides sustained VMAT2 inhibition with once-daily dosing.
| Attribute |
Details |
| Company |
Teva Pharmaceutical |
| Product |
Austedo |
| Indication |
Huntington's disease, Tardive Dyskinesia |
| Mechanism |
VMAT2 inhibitor (deuterated) |
| Status |
Approved 2017 |
Deutetrabenazine uses deuterium substitution to improve pharmacokinetics and reduce dosing frequency compared to tetrabenazine.
While VMAT2 inhibitors are not approved for PD, they have potential applications:
| Application |
Rationale |
| Dyskinesia management |
Reduce dopamine signaling |
| OFF episode control |
Modulate dopamine release |
| Combination therapy |
Adjunct to levodopa |
| Company |
Focus |
Stage |
| Neurocrine |
HD chorea → PD potential |
Phase 3 |
| Teva |
TD in PD patients |
Research |
| Various |
Novel VMAT2 modulators |
Discovery |
VMAT2 inhibitors work by:
- Blocking vesicular dopamine packaging
- Reducing quantal dopamine release
- Decreasing synaptic dopamine levels
| Disorder |
Effect |
| Tardive Dyskinesia |
Reduces involuntary movements |
| Huntington's Disease |
Reduces chorea |
| Potential PD |
May reduce dyskinesia |
Several companies are developing next-generation VMAT2 targeting compounds:
| Company |
Program |
Focus |
Stage |
| Neurocrine |
Valbenazine extensions |
HD, PD |
Phase 3 |
| Teva |
Deutetrabenazine analogs |
Improved PK |
Preclinical |
| Research institutions |
VMAT2 PET agents |
Imaging |
Research |
| Company |
Product |
Application |
| Life Molecular Imaging |
VMAT2 PET tracers |
Diagnostic imaging |
| Roche |
VMAT2 ligands |
Research |
| Target |
Mechanism |
PD Application |
| VMAT2 |
Reduce dopamine release |
Emerging (dyskinesia) |
| MAO-B |
Block dopamine breakdown |
Established (Azilect, Zelapar) |
| COMT |
Block peripheral metabolism |
Established (Ongentys, Stalevo) |
| DAT |
Block reuptake |
Research |
| D1/D2 receptors |
Direct activation |
Established (agonists) |