VMAT2 substrate (vesicular release)
VMAT2 substrate causing vesicular monoamine release
- Enters and alkalinizes vesicles → reverses VMAT2 transport
- Monoamines flood the cytoplasm → massive synaptic release if paired with DAT/NET reversal
- The opposite of VMAT2 inhibition: release, not depletion
- Transported INTO the vesicle, alkalinizing it and driving reverse transport
- ➔ monoamine floods the cytoplasm and exits through DAT/NET
- ⚑ Opposite outcome to VMAT2 inhibition: massive synaptic release, not depletion
- Underlies the euphoria and neurotoxicity of amphetamine-type stimulants
Drugs with this mechanism (1)
- Methamphetamine — Potent, CNS-penetrant amphetamine; high addiction liability, rare medical use.
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