Tetrabenazine (TBZ)
Part 1

How does TBZ work?

Recall that chorea is believed to be caused by increased activity of the neurotransmitter dopamine. TBZ exerts its anti-choreic effects by reducing the amount of dopamine in the brain in two ways. One is by preventing dopamine from being released in the first place. At the end of each nerve cell, neurotransmitters such as dopamine are stored in containers called vesicles, which are transported to the ends of nerve cells for release through the membrane into the synapse. Special molecules called vesicular monoamine transporters (VMATs) are responsible for putting the neurotransmitters into these vesicles. TBZ binds to the VMATs, preventing them from performing this function. As such, neurotransmitters like dopamine are not stored in vesicles or released into the synapse, where they would otherwise affect other nerve cells.

The second way that TBZ reduces dopamine is by blocking dopamine receptors. TBZ binds to the receptors on the surface of the receiving nerve cell, blocking dopamine from binding and passing on its message. (For more information on the neurobiology of HD, click here.) Because it blocks dopamine on both sides of the synapse, TBZ is thought to be that much more effective at treating choreonic movement disorders.

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Last Modified: 1-25-06

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