Valbenazine

Valbenazine

Clinical data
Trade names	Ingrezza
Synonyms	NBI-98854
AHFS/Drugs.com	ingrezza
Routes of administration	By mouth
ATC code	none
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Protein binding	>99%
Metabolism	Activation by hydrolysis, deactivation by CYP3A, CYP2D6
Metabolites	[+]-α-Dihydrotetrabenazine (active metabolite)
Biological half-life	15–22 hrs
Excretion	60% urine, 30% faeces
Identifiers
IUPAC name (2R,3R,11bR)-3-Isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl L-valinate
CAS Number	1025504-45-3 Y
PubChem CID	24795069
DrugBank	DB11915 Y
ChemSpider	28536134 Y
UNII	54K37P50KH
KEGG	D10675 Y
ChEMBL	CHEMBL2364639 Y
Chemical and physical data
Formula	C24H38N2O4
Molar mass	418.58 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(C)C[C@@H]1CN2CCc3cc(c(cc3[C@H]2C[C@H]1OC(=O)[C@H](C(C)C)N)OC)OC
InChI InChI=InChI=1S/C24H38N2O4/c1-14(2)9-17-13-26-8-7-16-10-21(28-5)22(29-6)11-18(16)19(26)12-20(17)30-24(27)23(25)15(3)4/h10-11,14-15,17,19-20,23H,7-9,12-13,25H2,1-6H3/t17-,19-,20-,23+/m1/s1 Y Key:GEJDGVNQKABXKG-CFKGEZKQSA-N Y

Valbenazine, sold under the trade name Ingrezza, is a medication use to treat tardive dyskinesia. It acts as a vesicular monoamine transporter 2 (VMAT2) inhibitor.

Valbenazine is used to treat tardive dyskinesia in adults.

There are no contraindications for valbenazine according to the prescribing information.

Valbenazine has not been effectively studied in pregnancy, and it is recommended that women who are pregnant or breastfeeding avoid use of valbenazine.

Side effects may include sleepiness or QT prolongation. Significant prolongation has not yet been observed at recommended dosage levels, however, those taking inhibitors of the liver enzymes CYP2D6 or CYP3A4 – or who are poor CYP2D6 metabolizers – may be at risk for significant prolongation.

Valbenazine is known to cause reversible reduction of dopamine 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 for VMAT1 or other monoamine receptors. Although the exact cause of tardive dyskinesia is unknown, it is hypothesized that it may result from neuroleptic-induced dopamine hypersensitivity. 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. The importance of valbenazine selectivity inhibiting VMAT2 over other monoamine transporters is that VMAT2 is mainly involved with the transport of dopamine, and to a much lesser extent other monoamines such as norepinephrine, serotonin, and histamine. This selectivity is likely to reduce the likelihood of "off-target" adverse effects which may result from the upstream inhibition of these other monoamines.