Tardivex is a uniquely selective VMAT2 inhibitor1,2

Tardivex is a uniquely selective VMAT2 inhibitor1,2

Tardive dyskinesia (TD)

TD—an often persistent movement disorder induced by prolonged DRBA exposure4

MOA of Tardivex (valbenazine) capsules

    1. VMAT2 plays a key role in dopamine signaling2

      • VMAT2 is a transporter protein found in presynaptic neurons of the CNS
      • VMAT2 packages monoamines (eg, dopamine) for release into the synaptic cleft

    2. TD is associated with prolonged exposure to DRBAs, including antipsychotics4

  • 3. Prolonged exposure to DRBAs can cause hypersensitivity in postsynaptic dopamine D2 receptors in areas that control motor function2

CNS, central nervous system; DRBA, dopamine receptor blocking agent; VMAT2, vesicular monoamine transporter 2.

 

1.  Selective inhibition of VMAT2 in presynaptic neurons, with no appreciable binding affinity for VMAT1, dopaminergic receptors, or serotonergic receptors2

2. Tardivex is believed to provide reversible reductions of dopamine release into the synaptic cleft2

3. Tardivex is believed to reduce the amount of dopamine available to hypersensitive postsynaptic dopamine D2 receptors1,2

CNS, central nervous system; DRBA, dopamine receptor blocking agent; VMAT2, vesicular monoamine transporter 2.

REFERENCES: 

  1. Harriott ND, Williams JP, Smith EB, Bozigian HP, Grigoriadis DE. VMAT2 inhibitors and the path to Tardivex (valbenazine). Prog Med Chem. 2018;57(1):87-111.
  2. Grigoriadis DE, Smith E, Hoare SRJ, Madan A, Bozigian H. Pharmacologic characterization of valbenazine (NBI-98854) and its metabolites. J Pharmacol Exp Ther. 2017;361(3):454-461.
  3. Hauser RA, Factor SA, Marder SR, et al. KINECT 3: a phase 3 randomized, double-blind, placebo-controlled trial of valbenazine for tardive dyskinesia. Am J Psychiatry. 2017;174(5):476-484.
  4. Coppen EM, Roos RA. Current pharmacological approaches to reduce chorea in Huntington’s disease. Drugs. 2017;77(1):29-46.
  5. Vesicular monoamine transporter 2 (VMAT2) inhibitors. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Accessed March 10, 2023. https://www.ncbi.nlm.nih.gov/books/NBK548187/?report=reader.
  6. Brar S, Vijan A, Scott FL, et al. Pharmacokinetic and pharmacologic characterization of the dihydrotetrabenazine isomers of deutetrabenazine and valbenazine. Clin Pharmacol Drug Dev. 2023;12(4):447-456.
  7. Skor H, Smith EB, Loewen G, O’Brien CF, Grigoriadis DE, Bozigian H. Differences in dihydrotetrabenazine isomer concentrations following administration of tetrabenazine and valbenazine. Drugs R D. 2017;17(3):449-459.
  8. Stahl SM. Comparing pharmacologic mechanism of action for the vesicular monoamine transporter 2 (VMAT2) inhibitors valbenazine and deutetrabenazine in treating tardive dyskinesia: does one have advantages over the other? CNS Spectr. 2018;23(4):239-247.
  9. Data on file. Neurocrine Biosciences, Inc.
  10. Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia. 3rd ed. American Psychiatric Association Publishing, 2020.
  11. Bhidayasiri R, Jitkritsadakul O, Friedman JH, Fahn S. Updating the recommendations for treatment of tardive syndromes: a systematic review of new evidence and practical treatment algorithm. J Neurol Sci. 2018;389:67-75.
  12. Caroff SN, Citrome L, Meyer J, et al. A modified Delphi consensus study of the screening, diagnosis, and treatment of tardive dyskinesia. J Clin Psychiatry. 2020;81(2):19cs12983.