Page last updated: 2024-12-07

dihydrotetrabenazine

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Description

dihydrotetrabenazine: RN given refers to cpd without isomeric designation [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID123836
CHEMBL ID4206824
CHEBI ID174330
SCHEMBL ID237573
SCHEMBL ID24674521
MeSH IDM0102082

Synonyms (56)

Synonym
9,10-dimethoxy-3-(2-methylpropyl)-2,3,4,6,7,11b-hexahydro-1h-benzo[a]quinolizin-2-ol
3466-75-9
CHEBI:174330
b-dihydrotetrabenazine
dihydrotetrabenazine
FT-0667059
2h-benzo(a)quinolizin-2-ol, 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-
2-hydroxy-3-isobutyl-9,10-dimethoxy-1,2,3,4,6,7-hexahydro-11bh-benzo(a)quinolizine
2-hydroxytetrabenazine
[3h]-tbzoh
[3h]dihydrotetrabenazine
9,10-dimethoxy-3-(2-methylpropyl)-2,3,4,6,7,11b-hexahydro-1h-pyrido[2,1-a]isoquinolin-2-ol
[3h]tbzoh
alpha-[o-methyl-3h]dihydrotetrabenazine
gtpl4766
SCHEMBL237573
AKOS027326401
9,10-dimethoxy-3-(2-methylpropyl)-1,3,4,6,7,11b-hexahydrobenzo[a]quinolizin-2-ol
FT-0774026
3-isobutyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1h-pyrido[2,1-a]isoquinolin-2-ol
(2r,3r,11bs)-dihydrotetrabenazine
(2r,3s,11br)-dihydrotetrabenazine
FT-0773772
(2s,3s,11bs)-9,10-dimethoxy-3-(2-methylpropyl)-1h,2h,3h,4h,6h,7h,11bh-pyrido[2,1-a]isoquinolin-2-ol
2h-benzo[a]quinolizin-2-ol, 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-, [2s-(2alpha,3beta,11bbeta)]-; (2s,3s,11bs)-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2h-benzo[a]quinolizin-2-ol
(+)-dtbz;(+)-alpha-dihydrotetrabenazine; (+)-alpha-dhtbz
(-)-beta-dihydrotetrabenazine;(-)-beta-htbz
nbi98782;nbi 98782;(+)-dtbz; (+)-(c) paragraph sign-dihydrotetrabenazine; (+)-(c) paragraph sign-dhtbz
BCP30240
(2r,3r,11bs)-9,10-dimethoxy-3-(2-methylpropyl)-1h,2h,3h,4h,6h,7h,11bh-pyrido[2,1-a]isoquinolin-2-ol
(2s,3r,11bs)-9,10-dimethoxy-3-(2-methylpropyl)-1h,2h,3h,4h,6h,7h,11bh-pyrido[2,1-a]isoquinolin-2-ol
(2r,3s,11br)-9,10-dimethoxy-3-(2-methylpropyl)-1h,2h,3h,4h,6h,7h,11bh-pyrido[2,1-a]isoquinolin-2-ol
862377-33-1
SB19833
SB18191
SB19834
SB19829
SB19830
SB19831
(2r,3r,11br)-9,10-dimethoxy-3-(2-methylpropyl)-1h,2h,3h,4h,6h,7h,11bh-pyrido[2,1-a]isoquinolin-2-ol
862377-31-9
SB18190
SB19832
862377-29-5
(+)-a-dhtbz
(+)-a-dihydrotetrabenazine
9,10-dimethoxy-3-(2-methylpropyl)-1,3,4,6,7,11b-hexahydro-2h-pyrido[2,1-a]isoquinolin-2-ol
DTXSID90956148
SY261801
(2r,3r,11br)-3-isobutyl-9,10-dimethoxy-2,3,4,6,7,11b-hexahydro-1h-pyrido[2,1-a]isoquinolin-2-ol
mfcd08061467
1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methylpropyl)-2h-benzo[a]quinolizin-2-ol
CHEMBL4206824 ,
bdbm50459619
SCHEMBL24674521
(+/-)-alpha-dihydrotetrabenazine

Research Excerpts

Overview

Dihydrotetrabenazine (TBZOH) is a very potent inhibitor of VMAT2 that binds with high affinity to this transporter.

ExcerptReferenceRelevance
"Dihydrotetrabenazine (TBZOH) is a very potent inhibitor of VMAT2 that binds with high affinity to this transporter."( Characterization of high-affinity [3H]TBZOH binding to the human platelet vesicular monoamine transporter.
Rehavi, M; Weizman, A; Zucker, M, 2001
)
1.03

Toxicity

ExcerptReferenceRelevance
" To verify this hypothesis, we investigated the influence of hypothermia on the toxic activity of both neurotoxins."( Apparent opposite effects of tetrabenazine and reserpine on the toxic effects of 1-methyl-4-phenylpyridinium or 6-hydroxydopamine on nigro-striatal dopaminergic neurons.
Cleren, C; Costentin, J; Naudin, B, 2003
)
0.32

Pharmacokinetics

ExcerptReferenceRelevance
" In both the patients and rats, the plasma profile of TBZ followed characteristics of a multiexponential pharmacokinetic model."( Pharmacokinetics of tetrabenazine and its major metabolite in man and rat. Bioavailability and dose dependency studies.
Jamali, F; Mehvar, R; Skelton, D; Watson, MW,
)
0.13
" The characteristics of high specific binding ratio, reversibility, metabolic stability and longer half-life of the radionuclide make [(18)F]FP-(+)-DTBZ a promising alternative VMAT2 radioligand suitable for widespread use in human positron emission tomography studies of monoaminergic innervation of the brain."( Pharmacokinetics of [(18)F]fluoroalkyl derivatives of dihydrotetrabenazine in rat and monkey brain.
Goswami, R; Hockley, B; Hou, C; Kilbourn, MR; Kung, HF; Kung, MP; Lee, L; Ponde, DE, 2007
)
0.59
" After method validation, an enantioselective in vitro metabolism and in vivo pharmacokinetic prediction was carried out."( In vitro enantioselective human liver microsomal metabolism and prediction of in vivo pharmacokinetic parameters of tetrabenazine by DLLME-CE.
Bocato, MZ; de Albuquerque, NCP; de Gaitani, CM; de Lima Moreira, F; de Oliveira, ARM, 2016
)
0.43

Dosage Studied

ExcerptRelevanceReference
"986 for TBZ and HTBZ, respectively, suggesting linear kinetics in the examined dosage range."( Pharmacokinetics of tetrabenazine and its major metabolite in man and rat. Bioavailability and dose dependency studies.
Jamali, F; Mehvar, R; Skelton, D; Watson, MW,
)
0.13
" The single high dose of MPTP produced greater losses of [(11)C]dihydrotetrabenazine binding than did the multiple MPTP dosing regimen."( Rapid and differential losses of in vivo dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) radioligand binding in MPTP-treated mice.
Kilbourn, MR; Kuszpit, K; Sherman, P, 2000
)
0.55
"Repeated dosing with alpha-methyl-p-tyrosine (AMPT) at doses that significantly (-75%) depleted brain tissue dopamine levels resulted in increased (+36%) in vivo [(11)C]DTBZ binding to VMAT2 in the striatum."( In vivo [11C]dihydrotetrabenazine binding in rat striatum: sensitivity to dopamine concentrations.
Butch, ER; Desmond, T; Frey, KA; Harris, PE; Kilbourn, MR; Sherman, P, 2010
)
0.73
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
isoquinolinesA class of organic heteropolycyclic compound consisting of isoquinoline and its substitution derivatives.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
5-hydroxytryptamine receptor 2AHomo sapiens (human)Ki0.00670.00000.385510.0000AID1387457
Synaptic vesicular amine transporterHomo sapiens (human)IC50 (µMol)0.02810.01320.48594.2000AID1387455
Synaptic vesicular amine transporterHomo sapiens (human)Ki3.40730.00530.83242.7600AID1387446; AID1387447; AID1387454
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Synaptic vesicular amine transporterHomo sapiens (human)Kd0.07100.00800.03950.0710AID1387453
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (57)

Processvia Protein(s)Taxonomy
temperature homeostasis5-hydroxytryptamine receptor 2AHomo sapiens (human)
positive regulation of cytokine production involved in immune response5-hydroxytryptamine receptor 2AHomo sapiens (human)
glycolytic process5-hydroxytryptamine receptor 2AHomo sapiens (human)
intracellular calcium ion homeostasis5-hydroxytryptamine receptor 2AHomo sapiens (human)
activation of phospholipase C activity5-hydroxytryptamine receptor 2AHomo sapiens (human)
positive regulation of cytosolic calcium ion concentration5-hydroxytryptamine receptor 2AHomo sapiens (human)
memory5-hydroxytryptamine receptor 2AHomo sapiens (human)
positive regulation of cell population proliferation5-hydroxytryptamine receptor 2AHomo sapiens (human)
response to xenobiotic stimulus5-hydroxytryptamine receptor 2AHomo sapiens (human)
positive regulation of phosphatidylinositol biosynthetic process5-hydroxytryptamine receptor 2AHomo sapiens (human)
regulation of dopamine secretion5-hydroxytryptamine receptor 2AHomo sapiens (human)
artery smooth muscle contraction5-hydroxytryptamine receptor 2AHomo sapiens (human)
urinary bladder smooth muscle contraction5-hydroxytryptamine receptor 2AHomo sapiens (human)
positive regulation of heat generation5-hydroxytryptamine receptor 2AHomo sapiens (human)
negative regulation of potassium ion transport5-hydroxytryptamine receptor 2AHomo sapiens (human)
phosphatidylinositol 3-kinase/protein kinase B signal transduction5-hydroxytryptamine receptor 2AHomo sapiens (human)
positive regulation of neuron apoptotic process5-hydroxytryptamine receptor 2AHomo sapiens (human)
protein localization to cytoskeleton5-hydroxytryptamine receptor 2AHomo sapiens (human)
positive regulation of fat cell differentiation5-hydroxytryptamine receptor 2AHomo sapiens (human)
positive regulation of glycolytic process5-hydroxytryptamine receptor 2AHomo sapiens (human)
positive regulation of vasoconstriction5-hydroxytryptamine receptor 2AHomo sapiens (human)
symbiont entry into host cell5-hydroxytryptamine receptor 2AHomo sapiens (human)
sensitization5-hydroxytryptamine receptor 2AHomo sapiens (human)
behavioral response to cocaine5-hydroxytryptamine receptor 2AHomo sapiens (human)
positive regulation of inflammatory response5-hydroxytryptamine receptor 2AHomo sapiens (human)
positive regulation of peptidyl-tyrosine phosphorylation5-hydroxytryptamine receptor 2AHomo sapiens (human)
detection of temperature stimulus involved in sensory perception of pain5-hydroxytryptamine receptor 2AHomo sapiens (human)
detection of mechanical stimulus involved in sensory perception of pain5-hydroxytryptamine receptor 2AHomo sapiens (human)
release of sequestered calcium ion into cytosol5-hydroxytryptamine receptor 2AHomo sapiens (human)
negative regulation of synaptic transmission, glutamatergic5-hydroxytryptamine receptor 2AHomo sapiens (human)
positive regulation of ERK1 and ERK2 cascade5-hydroxytryptamine receptor 2AHomo sapiens (human)
G protein-coupled serotonin receptor signaling pathway5-hydroxytryptamine receptor 2AHomo sapiens (human)
presynaptic modulation of chemical synaptic transmission5-hydroxytryptamine receptor 2AHomo sapiens (human)
positive regulation of execution phase of apoptosis5-hydroxytryptamine receptor 2AHomo sapiens (human)
positive regulation of platelet aggregation5-hydroxytryptamine receptor 2AHomo sapiens (human)
positive regulation of DNA biosynthetic process5-hydroxytryptamine receptor 2AHomo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger5-hydroxytryptamine receptor 2AHomo sapiens (human)
phospholipase C-activating serotonin receptor signaling pathway5-hydroxytryptamine receptor 2AHomo sapiens (human)
serotonin receptor signaling pathway5-hydroxytryptamine receptor 2AHomo sapiens (human)
chemical synaptic transmission5-hydroxytryptamine receptor 2AHomo sapiens (human)
response to amphetamineSynaptic vesicular amine transporterHomo sapiens (human)
serotonin secretion by mast cellSynaptic vesicular amine transporterHomo sapiens (human)
histamine secretion by mast cellSynaptic vesicular amine transporterHomo sapiens (human)
neurotransmitter transportSynaptic vesicular amine transporterHomo sapiens (human)
chemical synaptic transmissionSynaptic vesicular amine transporterHomo sapiens (human)
locomotory behaviorSynaptic vesicular amine transporterHomo sapiens (human)
response to toxic substanceSynaptic vesicular amine transporterHomo sapiens (human)
post-embryonic developmentSynaptic vesicular amine transporterHomo sapiens (human)
monoamine transportSynaptic vesicular amine transporterHomo sapiens (human)
dopamine transportSynaptic vesicular amine transporterHomo sapiens (human)
sequestering of neurotransmitterSynaptic vesicular amine transporterHomo sapiens (human)
serotonin uptakeSynaptic vesicular amine transporterHomo sapiens (human)
histamine uptakeSynaptic vesicular amine transporterHomo sapiens (human)
neurotransmitter loading into synaptic vesicleSynaptic vesicular amine transporterHomo sapiens (human)
somato-dendritic dopamine secretionSynaptic vesicular amine transporterHomo sapiens (human)
proton transmembrane transportSynaptic vesicular amine transporterHomo sapiens (human)
negative regulation of reactive oxygen species biosynthetic processSynaptic vesicular amine transporterHomo sapiens (human)
aminergic neurotransmitter loading into synaptic vesicleSynaptic vesicular amine transporterHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (13)

Processvia Protein(s)Taxonomy
Gq/11-coupled serotonin receptor activity5-hydroxytryptamine receptor 2AHomo sapiens (human)
virus receptor activity5-hydroxytryptamine receptor 2AHomo sapiens (human)
G protein-coupled serotonin receptor activity5-hydroxytryptamine receptor 2AHomo sapiens (human)
protein binding5-hydroxytryptamine receptor 2AHomo sapiens (human)
protein tyrosine kinase activator activity5-hydroxytryptamine receptor 2AHomo sapiens (human)
identical protein binding5-hydroxytryptamine receptor 2AHomo sapiens (human)
protein-containing complex binding5-hydroxytryptamine receptor 2AHomo sapiens (human)
serotonin binding5-hydroxytryptamine receptor 2AHomo sapiens (human)
1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding5-hydroxytryptamine receptor 2AHomo sapiens (human)
neurotransmitter receptor activity5-hydroxytryptamine receptor 2AHomo sapiens (human)
protein bindingSynaptic vesicular amine transporterHomo sapiens (human)
monoamine transmembrane transporter activitySynaptic vesicular amine transporterHomo sapiens (human)
monoamine:proton antiporter activitySynaptic vesicular amine transporterHomo sapiens (human)
serotonin:sodium:chloride symporter activitySynaptic vesicular amine transporterHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (22)

Processvia Protein(s)Taxonomy
neurofilament5-hydroxytryptamine receptor 2AHomo sapiens (human)
plasma membrane5-hydroxytryptamine receptor 2AHomo sapiens (human)
caveola5-hydroxytryptamine receptor 2AHomo sapiens (human)
axon5-hydroxytryptamine receptor 2AHomo sapiens (human)
cytoplasmic vesicle5-hydroxytryptamine receptor 2AHomo sapiens (human)
presynaptic membrane5-hydroxytryptamine receptor 2AHomo sapiens (human)
neuronal cell body5-hydroxytryptamine receptor 2AHomo sapiens (human)
dendritic shaft5-hydroxytryptamine receptor 2AHomo sapiens (human)
postsynaptic membrane5-hydroxytryptamine receptor 2AHomo sapiens (human)
cell body fiber5-hydroxytryptamine receptor 2AHomo sapiens (human)
glutamatergic synapse5-hydroxytryptamine receptor 2AHomo sapiens (human)
G protein-coupled serotonin receptor complex5-hydroxytryptamine receptor 2AHomo sapiens (human)
plasma membrane5-hydroxytryptamine receptor 2AHomo sapiens (human)
dendrite5-hydroxytryptamine receptor 2AHomo sapiens (human)
centrosomeSynaptic vesicular amine transporterHomo sapiens (human)
plasma membraneSynaptic vesicular amine transporterHomo sapiens (human)
synaptic vesicleSynaptic vesicular amine transporterHomo sapiens (human)
membraneSynaptic vesicular amine transporterHomo sapiens (human)
axonSynaptic vesicular amine transporterHomo sapiens (human)
dendriteSynaptic vesicular amine transporterHomo sapiens (human)
secretory granule membraneSynaptic vesicular amine transporterHomo sapiens (human)
synaptic vesicle membraneSynaptic vesicular amine transporterHomo sapiens (human)
intracellular membrane-bounded organelleSynaptic vesicular amine transporterHomo sapiens (human)
clathrin-sculpted monoamine transport vesicle membraneSynaptic vesicular amine transporterHomo sapiens (human)
dopaminergic synapseSynaptic vesicular amine transporterHomo sapiens (human)
terminal boutonSynaptic vesicular amine transporterHomo sapiens (human)
synaptic vesicle membraneSynaptic vesicular amine transporterHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (10)

Assay IDTitleYearJournalArticle
AID1387455Inhibition of human VMAT2 expressed in HEK293 cell membranes assessed as reduction in [3H[-5HT uptake pre-incubated for 10 mins before [3H[-5HT addition and measured after 6 mins2018Journal of medicinal chemistry, 10-25, Volume: 61, Issue:20
Synthesis and Discovery of Arylpiperidinylquinazolines: New Inhibitors of the Vesicular Monoamine Transporter.
AID1387454Displacement of [3H](+)-syn-Ethyl 1-(2-(2,4-Dioxo-1,2-dihydroquinazolin-3(4H)-yl)ethyl)-4-(4-fluorophenyl)piperidine-3-carboxylate from human VMAT2 expressed in HEK293 cell membranes incubated for 60 mins by scintillation counting method2018Journal of medicinal chemistry, 10-25, Volume: 61, Issue:20
Synthesis and Discovery of Arylpiperidinylquinazolines: New Inhibitors of the Vesicular Monoamine Transporter.
AID1387446Displacement of [3H]reserpine from human VMAT2 expressed in HEK293 cell membranes incubated for 60 mins by scintillation counting method2018Journal of medicinal chemistry, 10-25, Volume: 61, Issue:20
Synthesis and Discovery of Arylpiperidinylquinazolines: New Inhibitors of the Vesicular Monoamine Transporter.
AID1387456Inhibition of VMAT2 in C57Bl/6J mouse striatal membranes assessed as reduction in [3H[-5HT uptake pre-incubated for 10 mins before [3H[-5HT addition and measured after 8 mins2018Journal of medicinal chemistry, 10-25, Volume: 61, Issue:20
Synthesis and Discovery of Arylpiperidinylquinazolines: New Inhibitors of the Vesicular Monoamine Transporter.
AID1387462Cytotoxicity in HEK293 cells expressing human VMAT2 assessed as reduction in cell viability at 10 uM incubated for 24 hrs by MTT assay2018Journal of medicinal chemistry, 10-25, Volume: 61, Issue:20
Synthesis and Discovery of Arylpiperidinylquinazolines: New Inhibitors of the Vesicular Monoamine Transporter.
AID1387457Displacement of [125I]DOI from human 5HT2A receptor expressed in HEK293 cell membranes2018Journal of medicinal chemistry, 10-25, Volume: 61, Issue:20
Synthesis and Discovery of Arylpiperidinylquinazolines: New Inhibitors of the Vesicular Monoamine Transporter.
AID1387453Binding affinity to human VMAT2 expressed in HEK293 cell membranes by scintillation counting method based saturation binding assay2018Journal of medicinal chemistry, 10-25, Volume: 61, Issue:20
Synthesis and Discovery of Arylpiperidinylquinazolines: New Inhibitors of the Vesicular Monoamine Transporter.
AID1387448Binding affinity to human VMAT2 expressed in HEK293 cell membranes in presence of 2 mM Mg-ATP by scintillation counting method2018Journal of medicinal chemistry, 10-25, Volume: 61, Issue:20
Synthesis and Discovery of Arylpiperidinylquinazolines: New Inhibitors of the Vesicular Monoamine Transporter.
AID1387447Displacement of [3H]DHTB from human VMAT2 expressed in HEK293 cell membranes incubated for 90 mins by microbeta scintillation counting method2018Journal of medicinal chemistry, 10-25, Volume: 61, Issue:20
Synthesis and Discovery of Arylpiperidinylquinazolines: New Inhibitors of the Vesicular Monoamine Transporter.
AID1345057Human Vesicular monoamine transporter 2 (SLC18 family of vesicular amine transporters)1996The Journal of biological chemistry, Nov-01, Volume: 271, Issue:44
Active transport of acetylcholine by the human vesicular acetylcholine transporter.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (227)

TimeframeStudies, This Drug (%)All Drugs %
pre-199027 (11.89)18.7374
1990's46 (20.26)18.2507
2000's83 (36.56)29.6817
2010's65 (28.63)24.3611
2020's6 (2.64)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 20.86

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index20.86 (24.57)
Research Supply Index5.48 (2.92)
Research Growth Index4.70 (4.65)
Search Engine Demand Index23.28 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (20.86)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials4 (1.71%)5.53%
Reviews6 (2.56%)6.00%
Case Studies2 (0.85%)4.05%
Observational0 (0.00%)0.25%
Other222 (94.87%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]