Synaptic vesicle monoamine transporter 2 (VMAT2)

Synaptic vesicle monoamine transporter 2 (VMAT2) is an integral membrane protein primarily expressed in the central nervous system, where it is localized to the membranes of synaptic vesicles in monoaminergic neurons (UniProt P35439). Its fundamental role is the transport of monoamine neurotransmitters—such as dopamine, norepinephrine, serotonin, and histamine—from the cytosol into vesicles using a proton gradient (PubMed: 29055358). This sequestration is essential for both neurotransmitter storage prior to release and the protection of neurons from oxidative stress caused by the accumulation of cytosolic monoamines (PubMed: 24508055). VMAT2 is a validated therapeutic target for movement disorders characterized by excessive dopaminergic signaling, including tardive dyskinesia and Huntington's disease chorea (StatPearls: NBK546659). Pharmacological inhibitors like valbenazine and deutetrabenazine reduce the vesicular loading and subsequent release of dopamine, thereby dampening hyperkinetic symptoms (FDA: Ingrezza Label). Despite its therapeutic utility, VMAT2 inhibition can cause significant side effects, such as depression and parkinsonism, due to the depletion of monoamines across various brain regions (PubMed: 28832270).

Other names

Solute carrier family 18 member 2SLC18A2Vesicular amine transporter 2Monoamine transporterVAT2

Reversible or irreversible inhibition of the VMAT2 protein, which prevents the loading of monoamine neurotransmitters (dopamine, serotonin, norepinephrine, and histamine) from the cytosol into synaptic vesicles, leading to their depletion and reduced release into the synaptic cleft.