What are VMAT2 inhibitors?
Vesicular monoamine transporter 2 (VMAT2) inhibitors, which deplete dopamine at presynaptic striatal nerve terminals, are a class of drugs that have long been used to treat hyperkinetic movement disorders, but have recently gained more attention following their development for specific indications in the United States.
Is reserpine a VMAT2 inhibitor?
As such, reserpine is classified as a competitive monoamine uptake inhibitor at VMAT1 and VMAT2.
How do VMAT2 inhibitors work?
VMAT2 inhibitors block VMAT2 causing dopamine depletion in the central nervous system. VMAT2 is a protein that controls the amount of dopamine stored in the nerve cells and the amount released. Inhibiting VMAT2 leads to a lower amount of available dopamine, thereby reducing unwanted body movements.
How do VMAT inhibitors treat tardive dyskinesia?
Trimming dopamine release via VMAT2 inhibition in the motor striatum results in stronger “stop” signals and weaker “go,” signals and thus robust therapeutic effects in reducing the abnormal involuntary hyperkinetic movements of tardive dyskinesia.
Is tetrabenazine a VMAT2?
Tetrabenazine (tet” ra ben’ a zeen) is an inhibitor of synaptic vesicular monoamine transporter 2 (VMAT2), the inhibition of which causes a depletion of neuroactive monoamines (serotonin, norepinephrine and particularly dopamine) in nerve terminals.
What is VMAT2 gene?
The vesicular monoamine transporter 2 (VMAT2) has a range of functions in the central nervous system, from sequestering toxins to providing conditions for the quantal release of monoaminergic neurotransmitters.
What are examples of monoamines?
Monoamines refer to the particular neurotransmitters dopamine, noradrenaline and serotonin. Dopamine and noradrenaline are sometimes also referred to as catecholamines.
Where is VMAT2 located?
adrenal medulla
VMAT2 is primarily expressed in multiple monoaminergic cells in the brain, sympathetic nervous system, mast cells, and histamine containing cells in the gut19–20. VMAT1 and VMAT2 are co-expressed in chromaffin cells of the adrenal medulla.
What happens if you block VMAT?
More specifically, inhibition of VMAT2 may cause an increase in cytosolic catecholamine levels, which can result in an increase in efflux of catecholamines through the cell membrane, depleting catecholamine concentrations and causing increased oxidative stress and oxidative damage to the neuron.
Are tremors part of tardive dyskinesia?
Tardive dyskinesia (TD), characterized by oro-buccal-lingual stereotypy, can manifest in the form of akathisia, dystonia, tics, tremor, chorea, or as a combination of different types of abnormal movements.
Where is VMAT2 gene?
Chemical neuroanatomy of VMAT2-expressing central neurons VMAT2 is expressed in all monoaminergic neurons of the brain, including those expressing dopamine (DA), serotonin (5-HT), norepinephrine (NE), epinephrine (EPI), and histamine (HIS).