 | |
| Clinical data | |
|---|---|
| Trade names | Ingrezza |
| Other names | NBI-98854 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a617023 |
| License data | |
| Routes of administration | By mouth |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Protein binding | >99% |
| Metabolism | Activation byhydrolysis, deactivation byCYP3A,CYP2D6 |
| Metabolites | [+]-α-Dihydrotetrabenazine (active metabolite) |
| Eliminationhalf-life | 15–22 hrs |
| Excretion | 60% urine, 30% faeces |
| Identifiers | |
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| CAS Number | |
| PubChemCID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.236.234 |
| Chemical and physical data | |
| Formula | C24H38N2O4 |
| Molar mass | 418.578 g·mol−1 |
| 3D model (JSmol) | |
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Valbenazine, sold under the brand nameIngrezza, is amedication used to treattardive dyskinesia.[1] It acts as avesicular monoamine transporter 2 (VMAT2)inhibitor.[2]
Valbenazine is used to treattardive dyskinesia in adults.[1] Tardive dyskinesia is a drug-induced neurological injury characterized by involuntary movements.[3] The clinical trials that led to the approval of valbenazine by the USFood and Drug Administration (FDA) were six weeks in duration.[1] An industry-sponsored study has studied 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.[4]
There are no contraindications for the use of valbenazine according to the prescribing information.[1]
Side effects may includesleepiness orQT prolongation.[5] Significant prolongation has not yet been observed at recommended dosage levels, however, those taking inhibitors of the liver enzymesCYP2D6 orCYP3A4 – or who are poor CYP2D6 metabolizers – may be at risk for significant prolongation.[5]
Valbenazine has not been effectively studied in pregnancy, and it is recommended that women who are pregnant or breastfeeding avoid use of valbenazine.[5]
Valbenazine is known to cause reversible reduction ofdopamine release by selectively inhibiting pre-synaptic human vesicular monoamine transporter type 2 (VMAT2).In vitro, valbenazine shows great selectivity for VMAT2 and little to no affinity forVMAT1 or other monoamine receptors.[6] Although the exact cause of tardive dyskinesia is unknown, it is hypothesized that it may result fromneuroleptic-induced dopaminehypersensitivity because it is exclusively associated with the use of neuroleptic drugs.[7] By selectively reducing the ability of VMAT2 to load dopamine into synaptic vesicles,[8] the drug reduces overall levels of available dopamine in the synaptic cleft, ideally alleviating the symptoms associated withdopamine hypersensitivity. The importance of valbenazine selectivity inhibiting VMAT2 over othermonoamine transporters is that VMAT2 is mainly involved with the transport of dopamine, and to a much lesser extent other monoamines such asnorepinephrine,serotonin, andhistamine. This selectivity is likely to reduce the likelihood of "off-target" adverse effects which may result from theupstream inhibition of these other monoamines.[9]
Valbenazine is aprodrug which is anester of [+]-α-dihydrotetrabenazine (DTBZ) with the amino acidL-valine. It is extensivelyhydrolyzed to theactive metabolite DTBZ.Plasma protein binding of valbenazine is over 99%, and that of DTBZ is about 64%. Thebiological half-life of both valbenazine and 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 thefeces (30%).[10]
Valbenazine is produced byNeurocrine Biosciences. Valbenazine was the first medication approved by the FDA for the treatment oftardive dyskinesia, in April 2017.[11]
While Neurocrine Biosciences does not hold a final patent for valbenazine orelagolix, they do hold a patent for the VMAT2 inhibitor [9,10-dimethoxy-3-(2-methylpropyl)-1H,2H,3H,4H,6H,7H,11bH-pyrido-[2,1-a]isoquinolin-2-yl]methanol and related compounds, which includes valbenazine.[12]
TheInternational Nonproprietary Name (INN) isvalbenazine.[13]: 114
Valbenazine is being studied for the treatment ofTourette's syndrome.[14][15]
