valbenazine   

GtoPdb Ligand ID: 8694

Synonyms: Ingrezza® | NBI 98854 | NBI-98854
valbenazine is an approved drug (FDA (2017))
Compound class: Synthetic organic
Comment: Valbenazine is an analogue of tetrabenazine, which similarly selectively inhibits the monoamine transporter SLC18A2 (VMAT2). A search of patent literature reveals valbenazine as example 2-1 in US8357697 B2 [1].
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 74.02
Molecular weight 418.28
XLogP 3.88
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES COc1cc2c(cc1OC)CCN1C2CC(OC(=O)C(C(C)C)N)C(C1)CC(C)C
Isomeric SMILES COc1cc2c(cc1OC)CCN1[C@@H]2C[C@@H](OC(=O)[C@H](C(C)C)N)[C@@H](C1)CC(C)C
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
InChI Key GEJDGVNQKABXKG-CFKGEZKQSA-N
No information available.
Summary of Clinical Use
FDA breakthrough drug status for tardive dyskinesia (TD) was converted to full approval, as the first and only approved treatment for adults with this condition, in April 2017 [2].
Mechanism Of Action and Pharmacodynamic Effects
SLC18A2 (VMAT2) transports monoamines, particularly neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine, from cellular cytosol into synaptic vesicles. Prolongued use of typical antipsychotics or centrally acting dopamine receptor blocking antiemetics at high doses can predispose patients to the onset of tardive syndromes, such as tardive dyskinesia. Valbenazine acts to regulate the levels of dopamine release during nerve communication, with minimal impact on the other monoamines. This selectivity is predicted to reduce the off target side effects arising from excessive dopamine depletion.