Valbenazine

Overview

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.[1][2] WP

Uses, dosage and effects

Medical use

Valbenazine is used to treat tardive dyskinesia in adults. Tardive dyskinesia is a drug-induced neurological injury characterized by involuntary movements. The clinical trials that led to the approval of valbenazine by the US Food and Drug Administration (FDA) were six weeks in duration. 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.[1][3][4] WP

Risks and side effects

Contraindications

There are no contraindications for the use of valbenazine according to the prescribing information.[1] WP

Adverse effects

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.[5] WP

Valbenazine has not been effectively studied in pregnancy, and it is recommended that women who are pregnant or breastfeeding avoid use of valbenazine.[5] WP

Pharmacology

Mechanism of action

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 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. 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.[6–9] WP

Pharmacokinetics

Valbenazine is a prodrug which is an ester of [+]-α-dihydrotetrabenazine (DTBZ) with the amino acid L-valine. It is 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 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 the feces (30%).[10] WP

Research

Research

Valbenazine is being studied for the treatment of Tourette's syndrome.[11][12] WP

Legal status

Legal status

Valbenazine is produced by Neurocrine Biosciences. Valbenazine was the first medication approved by the FDA for the treatment of tardive dyskinesia, in April 2017.[13] WP

Economics

While Neurocrine Biosciences does not hold a final patent for valbenazine or elagolix, 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.[14] WP

Names

The International Nonproprietary Name (INN) is valbenazine.[15] WP

Chemistry

Formula

C24H38N2O4 PC

CAS number

1025504-45-3 PC

Molar mass (g/mol)

418.6 PC

IUPAC name (computed by PubChem)

[(2R,3R,11bR)-9,10-dimethoxy-3-(2-methylpropyl)-2,3,4,6,7,11b-hexahydro-1H-benzo[a]quinolizin-2-yl] (2S)-2-amino-3-methylbutanoate PC

SMILES

CC(C)C[C@@H]1CN2CCC3=CC(=C(C=C3[C@H]2C[C@H]1OC(=O)[C@H](C(C)C)N)OC)OC PC

InChIKey

GEJDGVNQKABXKG-CFKGEZKQSA-N PC

PubChem CID

24795069

IUPAC name

(2R,3R,11bR)-3-Isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido WP

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Ingrezza- valbenazine capsule; Ingrezza- valbenazine kit. 18 August 2023
2. Journal / agency O'Brien CF, Jimenez R, Hauser RA, Factor SA, Burke J, Mandri D, Castro-Gayol JC. NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: A randomized, double-blind, placebo-controlled study. Movement Disorders. October 2015. doi:10.1002/mds.26330 · PMID 26346941 · PMC5049616
3. Journal / agency Tardive dyskinesia. 1 June 2017
4. Other Janeczko, Lorraine. Long-term Valbenazine Appears Safe for Patients With Tardive Dyskinesia
5. Other Valbenazine: Drug Information
6. Other NBI-98854 – VMAT2 Inhibitor | Tics in Children Treatment | Neurocrine Biosciences
7. Other tardive-dyskinesia
8. Other Purves D, etal. Neuroscience. 2018
9. Other NBIX: NDA for Valbenazine in Tardive Dyskinesia to be Filed in 2016…
10. Other Valbenazine Drugs.com ppa valbenazine
11. Other Tourette Syndrome Clinical Trials
12. Other ClinicalTrialsGov NCT02581865 Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
13. Journal / agency Office of the Commissioner. Press Announcements - FDA approves first drug to treat tardive dyskinesia
14. Other 9,10-dimethoxy-3-(2-methylpropyl)-1h,2h,3h,4h,6h,7h,11bh-pyrido-[2,1-aisoquinolin-2-yl]methanol And Compounds, Compositions And Methods Relating Thereto
15. Journal / agency International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 71

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.