Tetrabenazine

Summary

Tetrabenazine (CHEMBL117785) is an approved small molecule (ATC N07XX06) targeting SLC18A1 and SLC18A2; indicated across 4 conditions including huntington disease and choreatic disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N07XX06
• Targets: 2 (SLC18A1, SLC18A2)
• Indications: 4 conditions
• Clinical trials: 9
• Chemistry: 317.4 Da · C19H27NO3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL117785
Name	Tetrabenazine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	6018
ChEBI	CHEBI:64028
ATC	N07XX06
Molecular formula	C19H27NO3
Molecular weight	317.4
InChIKey	MKJIEFSOBYUXJB-UHFFFAOYSA-N

SMILES: CC(C)CC1CN2CCC3=CC(=C(C=C3C2CC1=O)OC)OC

IUPAC name: 9,10-dimethoxy-3-(2-methylpropyl)-1,3,4,6,7,11b-hexahydrobenzo[a]quinolizin-2-one

ChEBI definition: A benzoquinolizine that is 1,2,3,4,4a,9,10,10a-octahydrophenanthrene in which the carbon at position 10a is replaced by a nitrogen and which is substituted by an isobutyl group at position 2, an oxo group at position 3, and methoxy groups at positions 6 and 7.

Also known as: Nitoman, NSC-169886, Revocon, RO-19569, Tetmodis, Tetrabenazina, Tetrabenazine, Xenazine, Xenazine 25, tetrabenazine, SID26753215, SID50086515

Parent form; salt/anhydrous children: CHEMBL3137326

Patent coverage: 2,641 distinct patent families (9,645 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 9,609 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
SLC18A1	Vesicular monoamine transporter 1	Inhibition	4.7	1%	P54219
SLC18A2	Vesicular monoamine transporter 2	Inhibition	7	0%	Q05940

Broader ChEMBL bioactivity targets: 17 (assay-derived). Sample: Microtubule-associated protein tau, Lysine-specific demethylase 4E, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Synaptic vesicular amine transporter, Thyrotropin receptor, Sodium channel alpha subunits; brain (Types I, II, III), 5-hydroxytryptamine receptor 1A, DNA polymerase beta, Serine/threonine-protein kinase mTOR, Aldehyde dehydrogenase 1A1, Mitogen-activated protein kinase 1, 3-hydroxyacyl-CoA dehydrogenase type-2, Synaptic vesicular amine transporter, Synaptic vesicular amine transporter, Bile salt export pump.

Bioactivity

ChEMBL activities: 11 potent at pChembl ≥ 5 of 25 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
Q27963	8.4	Ki	4	nM	CHEMBL_ACT_2100956
Q01827	8.15	AC50	7	nM	CHEMBL_ACT_25197398
Q01827	8.12	Ki	7.62	nM	CHEMBL_ACT_6178951
Q01827	7.96	IC50	10.98	nM	CHEMBL_ACT_23243469
Q01827	7.89	Ki	13	nM	CHEMBL_ACT_2922381
Q01827	7.89	Ki	13	nM	CHEMBL_ACT_3109088
SLC18A2	7.7	IC50	19.8	nM	CHEMBL_ACT_24930890
Q01827	7.27	Ki	54	nM	CHEMBL_ACT_2922401
Q01827	7.15	IC50	70.22	nM	CHEMBL_ACT_23243425
POLB	5.4	Potency	3981	nM	CHEMBL_ACT_4889588
HTR2B	5.07	AC50	8600	nM	CHEMBL_ACT_25227904

Target pathways

Aggregated over 2 target gene(s): SLC18A1, SLC18A2.

Top Reactome pathways

4 total, by targets touching each:

Pathway	Targets	Genes
SLC-mediated transport of neurotransmitters	2	SLC18A1, SLC18A2
Serotonin Neurotransmitter Release Cycle	1	SLC18A2
Norepinephrine Neurotransmitter Release Cycle	1	SLC18A2
Dopamine Neurotransmitter Release Cycle	1	SLC18A2

Dominant GO biological processes

GO term	Targets
aminergic neurotransmitter loading into synaptic vesicle	2
obsolete monoamine transport	2
obsolete dopamine transport	2
serotonin uptake	2
neurotransmitter transport	2
obsolete serotonin transport	2
xenobiotic transport	2
establishment of localization in cell	2
transmembrane transport	2
proton transmembrane transport	2
norepinephrine uptake	1
dopamine uptake	1
response to amphetamine	1
serotonin secretion by mast cell	1
histamine secretion by mast cell	1

Indications & clinical

Indications

2 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
Huntington disease	4	MONDO:0007739	MONDO:0007739
choreatic disease	4	MONDO:0001595	EFO:0004152

2 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
movement disorder	3	MONDO:0005395	EFO:0004280
Tourette syndrome	2	MONDO:0007661	EFO:0004895

Clinical trials

Total trials: 9.

Phase distribution

Phase	Trials
PHASE4	3
PHASE3	2
PHASE1	2
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01834911	PHASE4	COMPLETED	Effect of Tetrabenazine on Stroop Interference in HD
NCT02509793	PHASE4	UNKNOWN	A Pilot Study Assessing Impulsivity in Patients With Huntington’s Disease on Xenazine (Tetrabenazine)
NCT04523935	PHASE4	COMPLETED	Excessive Crying in Children With Cerebral Palsy and Communication Deficits
NCT00632645	PHASE3	COMPLETED	Neuroleptic and Huntington Disease Comparison of : Olanzapine, la Tetrabenazine and Tiapride
NCT01543321	PHASE3	COMPLETED	Xenazine in Late Dyskinetic Syndrome With Neuroleptics
NCT03696329	PHASE1	COMPLETED	Bioequivalence Study of Tetrabenazine Tablets 25 mg Under Fasting Conditions
NCT03702855	PHASE1	COMPLETED	Bioequivalence Study of Tetrabenazine Tablets 25 mg Under Fed Conditions
NCT00362804	Not specified	COMPLETED	Tetrabenazine for Partial Responders
NCT00642057	Not specified	NO_LONGER_AVAILABLE	Compassionate Use of Tetrabenazine in the Treatment of Abnormal Movements

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 4 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

5 molecules share ≥1 primary target. Top 5 by shared-target count:

Molecule	Source	Status	Shared targets
RESERPINE	ChEMBL + PubChem	Phase 4 (approved)	SLC18A1, SLC18A2
KETANSERIN	ChEMBL	Phase 4 (approved)	SLC18A2
SEROTONIN	ChEMBL + PubChem	Phase 3 (approved)	SLC18A2
FLORBENAZINE	ChEMBL	Phase 2	SLC18A2
LOBELINE	ChEMBL	Phase 2	SLC18A2