Valbenazine
Pharmacology
Pharmacology
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### Mechanism of action

Valbenazine is known to cause reversible reduction of [dopamine](/wiki/Dopamine "Dopamine") release by selectively inhibiting pre\-synaptic human vesicular monoamine transporter type 2 (VMAT2\). *[In vitro](/wiki/In_vitro "In vitro")*, valbenazine shows great selectivity for VMAT2 and little to no affinity for [VMAT1](/wiki/Vesicular_monoamine_transporter_1 "Vesicular monoamine transporter 1") or other monoamine receptors. Although the exact cause of tardive dyskinesia is unknown, it is hypothesized that it may result from [neuroleptic](/wiki/Antipsychotic "Antipsychotic")\-induced dopamine [hypersensitivity](/wiki/Upregulation "Upregulation") because it is exclusively associated with the use of neuroleptic drugs. By selectively reducing the ability of VMAT2 to load dopamine into synaptic vesicles, the drug reduces overall levels of available dopamine in the synaptic cleft, ideally alleviating the symptoms associated with [dopamine hypersensitivity](/wiki/Dopamine_hypersensitivity "Dopamine hypersensitivity"). The importance of valbenazine selectivity inhibiting VMAT2 over other [monoamine transporters](/wiki/Monoamine_transporter "Monoamine transporter") is that VMAT2 is mainly involved with the transport of dopamine, and to a much lesser extent other monoamines such as [norepinephrine](/wiki/Norepinephrine "Norepinephrine"), [serotonin](/wiki/Serotonin "Serotonin"), and [histamine](/wiki/Histamine "Histamine"). This selectivity is likely to reduce the likelihood of "off\-target" adverse effects which may result from the [upstream](/wiki/Upstream_%28bioprocess%29 "Upstream (bioprocess)") inhibition of these other monoamines.

### Pharmacokinetics

Valbenazine is a [prodrug](/wiki/Prodrug "Prodrug") which is an [ester](/wiki/Ester "Ester") of \[\+]\-α\-[dihydrotetrabenazine](/wiki/Dihydrotetrabenazine "Dihydrotetrabenazine") (DTBZ) with the amino acid L\-[valine](/wiki/Valine "Valine"). It is extensively [hydrolyzed](/wiki/Hydrolyzed "Hydrolyzed") to the [active metabolite](/wiki/Active_metabolite "Active metabolite") DTBZ. [Plasma protein binding](/wiki/Plasma_protein_binding "Plasma protein binding") of valbenazine is over 99%, and that of DTBZ is about 64%. The [biological half\-life](/wiki/Biological_half-life "Biological half-life") of both valbenazine and DTBZ is 15 to 22 hours. Liver enzymes involved in inactivation are CYP3A4, [CYP3A5](/wiki/CYP3A5 "CYP3A5") and CYP2D6\. The drug is excreted, mostly in form of inactive metabolites, via the urine (60%) and the [feces](/wiki/Feces "Feces") (30%).Valbenazine .


What are the pharmacokinetic properties of valbenazine?