Small molecule
PubChem CID 24795069
Valbenazine
Ingrezza
- Mechanism of action
- VMAT2 inhibitor (prodrug)
- In plain language
- Turns into an active form in the body that quiets down dopamine release from nerve cells, easing the involuntary movements of tardive dyskinesia and Huntington's disease chorea.
- How it works
- Valbenazine is an orally administered prodrug that is rapidly hydrolyzed to its active metabolite, [+]-alpha-dihydrotetrabenazine, primarily via ester hydrolysis, with additional oxidative metabolism mediated by CYP3A4/5. The active metabolite is a selective, reversible inhibitor of vesicular monoamine transporter 2 (VMAT2), the transporter responsible for packaging dopamine and other monoamines from the cytoplasm into synaptic vesicles for storage and release. By reducing VMAT2-mediated vesicular loading, valbenazine's active metabolite decreases presynaptic dopamine release. This presynaptic mechanism is distinct from antipsychotic drugs, which act postsynaptically by blocking dopamine receptors — a distinction relevant because tardive dyskinesia is thought to arise from postsynaptic dopamine receptor supersensitivity following chronic antipsychotic exposure. Per FDA labeling, the precise mechanism by which VMAT2 inhibition produces clinical benefit in tardive dyskinesia and Huntington's disease chorea remains formally unclear.
- Therapeutic applications
- Per FDA-approved labeling, valbenazine (Ingrezza / Ingrezza Sprinkle) is indicated for the treatment of adults with tardive dyskinesia and for chorea associated with Huntington's disease. Tardive dyskinesia was the original approved indication (2017); the Huntington's disease chorea indication was approved separately in 2023, based on the KINECT-HD trial program.
- Class
- Small molecule
- Therapeutic area
- Neurology
View
Related compounds