VMAT2 inhibitors approved for tardive dyskinesia work by what mechanism?

VMAT2 inhibitors approved for tardive dyskinesia work by what mechanism?

• A. Increasing dopamine release
• B. Blocking D2 receptors
• C. Decreasing dopamine release
• D. Inhibiting serotonin synthesis

Answer: (C)

Reducing presynaptic dopamine release is the mechanism at work. VMAT2 inhibitors block the vesicular monoamine transporter 2, which normally loads dopamine into synaptic vesicles for release. When VMAT2 is inhibited, fewer dopamine molecules are packaged, so each neuronal firing releases less dopamine into the synapse. This dampens dopaminergic signaling in motor circuits, helping to lessen tardive dyskinesia symptoms. This approach targets the presynaptic supply rather than directly blocking dopamine receptors, and it doesn’t affect serotonin synthesis. Drugs in this class, such as valbenazine and deutetrabenazine, exemplify this mechanism.

Reducing presynaptic dopamine release is the mechanism at work. VMAT2 inhibitors block the vesicular monoamine transporter 2, which normally loads dopamine into synaptic vesicles for release. When VMAT2 is inhibited, fewer dopamine molecules are packaged, so each neuronal firing releases less dopamine into the synapse. This dampens dopaminergic signaling in motor circuits, helping to lessen tardive dyskinesia symptoms. This approach targets the presynaptic supply rather than directly blocking dopamine receptors, and it doesn’t affect serotonin synthesis. Drugs in this class, such as valbenazine and deutetrabenazine, exemplify this mechanism.