Valbenazine, sold under the brand name Ingrezza, is a medication used to treat tardive dyskinesia.
It acts as a vesicular monoamine transporter 2 (VMAT2) inhibitor.
Routes of administration-By mouth
Protein binding >99%
Activation by hydrolysis, deactivation by CYP3A, CYP2D6
Elimination half-life 15–22 hrs
Excretion 60% urine, 30% faeces
Valbenazine is used to treat tardive dyskinesia in adults.
Tardive dyskinesia is a drug-induced neurological injury characterized by involuntary movements.
Studies in the use of valbenazine for up to 48 weeks, in which it was found to be safe and effective for maintaining short-term, 6 week, improvements in tardive dyskinesia.
Adverse effects: sleepiness, QT prolongation in those taking inhibitors of the liver enzymes CYP2D6 or CYP3A4 – or who are poor CYP2D6 metabolizers.
Not been effectively studied in pregnancy, and it is recommended that women who are pregnant or breastfeeding avoid use of valbenazine.
It causes reversible reduction of dopamine release by selectively inhibiting pre-synaptic human vesicular monoamine transporter type 2 (VMAT2).
Tardive dyskinesia, it is hypothesized that it may result from neuroleptic-induced dopamine hypersensitivity because it is exclusively associated with the use of neuroleptic drugs.
By the selectional reduction in 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.
It is mainly involved with the transport of dopamine, and to a much lesser extent other monoamines such as norepinephrine, serotonin, and histamine.
Valbenazine is a prodrug which is and is s extensively hydrolyzed to the active metabolite DTBZ.
Plasma protein binding of valbenazine is over 99%, and that of DTBZ is about 64%.
The biological half-life of both valbenazine/ DTBZ is 15 to 22 hours.
Liver enzymes involved in inactivation are CYP3A4, CYP3A5 and CYP2D6.
The drug is excreted, mostly in form of inactive metabolites, via the urine (60%) and the feces (30%).
Valbenazine is being studied for the treatment of Tourette’s syndrome.