The vesicular monoamine transporter (VMAT) is a transport protein

Transport protein

A membrane transport protein is a membrane protein involved in the movement of ions, small molecules, or macromolecules, such as another protein across a biological membrane. Transport proteins are integral membrane proteins; that is they exist within and span the membrane across which they...

 integrated into the membrane of intracellular vesicles of presynaptic neurons

Synapse

In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...

. It acts to transport monoamines into the synaptic vesicle

Synaptic vesicle

In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...

s.

Monoamines

Monoamines transported by VMATs are mainly noradrenaline, adrenaline and isoprenaline. However, other substrates include dopamine

Dopamine

Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

, 5-HT, guanethidine

Guanethidine

Guanethidine is an antihypertensive drug that reduces the release of catecholamines, such as norepinephrine. Guanethidine is transported across the sympathetic nerve membrane by the same mechanism that transports norepinephrine itself , and uptake is essential for the drug's action...

 and MPP+

MPP+

MPP+ is a positively charged molecule with chemical formula C12H12N+. It is toxic and acts by interfering with oxidative phosphorylation in mitochondria, causing depletion of ATP and cell death...

.

Clinical significance

VMAT can be inhibited by reserpine

Reserpine

Reserpine is an indole alkaloid antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely...

, tetrabenazine

Tetrabenazine

Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorder and is marketed under the trade names Nitoman in Canada and Xenazine in New Zealand and some parts of Europe, and is also available in the USA as an orphan drug. On August 15, 2008 the U.S...

 and ibogaine

Ibogaine

Ibogaine is a naturally occurring psychoactive substance found in a number of plants, principally in a member of the Apocynaceae family known as Iboga . A hallucinogen with both psychedelic and dissociative properties, the substance is banned in some countries; in other countries it is being used...

.

VMAT is the main target of methamphetamine

Methamphetamine

Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...

. By acting as a competitive antagonist

Competitive antagonist

A competitive antagonist is a receptor antagonist that binds to a receptor but does not activate the receptor. The antagonist will compete with available agonist for receptor binding sites on the same receptor...

, methamphetamine blocks the presynaptic cell's ability to use VMAT to package the above mentioned neurotransmitters into vesicles. The result is increased neurotransmitter release that is not dependent on the phasic activity of the presynaptic cell.

Further reading