Solute carrier family 18 member 2 (VMAT2) (VMAT2)

The Human Vesicular Monoamine Transporter 2 (VMAT2), encoded by the SLC18A2 gene, is an integral membrane protein essential for the regulation of monoaminergic neurotransmission in the central nervous system [1, 3]. It functions as a proton-dependent antiporter that packages monoamine neurotransmitters, such as dopamine, serotonin, norepinephrine, and histamine, from the neuronal cytosol into synaptic vesicles for subsequent exocytotic release [2, 11]. Beyond its role in neurotransmission, VMAT2 provides critical neuroprotection by sequestering potentially toxic cytosolic monoamines, thereby preventing oxidative stress and neuronal damage [8, 15]. Dysregulation or reduced expression of VMAT2 is associated with neurodegenerative conditions like Parkinson's disease, while excessive dopaminergic activity facilitated by VMAT2 is linked to hyperkinetic movement disorders such as Huntington's chorea and tardive dyskinesia [6, 11]. Pharmacological inhibitors, including tetrabenazine, deutetrabenazine, and valbenazine, are used clinically to deplete monoamine stores and alleviate hyperkinetic symptoms [9, 12]. Additionally, VMAT2 is a key site of action for psychostimulants like amphetamines and MDMA, which can disrupt its normal function to increase synaptic monoamine levels [1, 4].

Other names

SLC18A2Vesicular monoamine transporter 2SVATSVMTVAT2Synaptic vesicular amine transporterPKDYS2

VMAT2 inhibitors act by reversibly binding to the transporter, preventing the uptake of cytosolic monoamines into synaptic vesicles and leading to the depletion of monoamine stores in nerve terminals [5, 9]. Substrates like amphetamines can also interact with VMAT2 to induce the release of sequestered monoamines into the cytosol [1, 2].