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Dihydrotetrabenazine
Identifiers
ChemSpider
InChI=1S/C19H29NO3/c1-12(2)7-14-11-20-6-5-13-8-18(22-3)19(23-4)9-15(13)16(20)10-17(14)21/h8-9,12,14,16-17,21H,5-7,10-11H2,1-4H3
Key: WEQLWGNDNRARGE-UHFFFAOYSA-N
COC1=C(OC)C=C(C(CC(O)C(CC(C)C)C2)N2CC3)C3=C1
Properties
C 19 H 29 N O 3
Molar mass
319.445 g·mol−1
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
Dihydrotetrabenazine or DTBZ is an
organic compound with the
chemical formula C19 H29 NO3 . It is a close analog of
tetrabenazine . DTBZ and its derivatives, when labeled with
positron emitting isotopes such as
carbon-11 and
fluorine-18 , are used as
PET
radioligands for examining
VMAT2 .
[1]
Use in Positron Emission Tomography
Carbon-11 labeled (+)DTBZ(right) and fluorine-18 labeled fluoropropylated (+)DTBZ(left)
Reconstructed data from PET scan of healthy human brain using [18 F]Fluoropropyl-DTBZ indicating
VMAT2 distribution
[2] [11 C]DTBZ as a PET radioligand with affinity for VMAT2 was developed in the mid 1990s by
David E. Kuhl and colleagues at the
University of Michigan .
[3] There are two
enantiomers of alpha-dihydrotetrabenazine, and the
dextrorotary (or (+) isomer) has a high
affinity of about 1 nanomolar Ki whereas the
levorotary (or (-) isomer) has approximately 1000 fold lower affinity with a Ki of about 2 micromolar.
[4]
VMAT2 is a membrane bound protein and a
biomarker for
Parkinson's disease . Binding of DTBZ to VMAT2 in individuals with
Parkinson's disease is significantly reduced.
[5] Moreover, the VMAT2 density as determined by [18 F]DTBZ has been shown to be well, inversely correlated with the severity of
Parkinson's disease .
[6]
Avid Radiopharmaceuticals has sponsored clinical trials of [18 F]AV-133 (or [18 F]Fluoropropyl-(+)-DTBZ) to identify subjects with dopaminergic degeneration.
[7]
See also
References
^ Koeppe, RA; Gilman, S; Joshi, A; Liu, S; Little, R; Junck, L; Heumann, M; Frey, KA; Albin, RL (June 2005). "11C-DTBZ and 18F-FDG PET measures in differentiating dementias". Journal of Nuclear Medicine . 46 (6): 936–44.
PMID
15937303 .
^ Lin, KJ; Weng, YH; Hsieh, CJ; Lin, WY; Wey, SP; Kung, MP; Yen, TC; Lu, CS; Hsiao, IT (2013).
"Brain imaging of vesicular monoamine transporter type 2 in healthy aging subjects by 18F-FP-(+)-DTBZ PET" . PLOS ONE . 8 (9): e75952.
Bibcode :
2013PLoSO...875952L .
doi :
10.1371/journal.pone.0075952 .
PMC
3786914 .
PMID
24098749 .
^ Frey, KA; Koeppe, RA; Kilbourn, MR; Vander Borght, TM; Albin, RL; Gilman, S; Kuhl, DE (December 1996).
"Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging" (PDF) . Annals of Neurology . 40 (6): 873–84.
doi :
10.1002/ana.410400609 .
hdl :
2027.42/50362 .
PMID
9007092 .
S2CID
9419161 .
^ Kilbourn, M; Lee, L; Vander Borght, T; Jewett, D; Frey, K (24 May 1995). "Binding of alpha-dihydrotetrabenazine to the vesicular monoamine transporter is stereospecific". European Journal of Pharmacology . 278 (3): 249–52.
doi :
10.1016/0014-2999(95)00162-e .
PMID
7589162 .
^ Wang, Jian; Hoekstra, Jake G.; Zuo, Chuantao; Cook, Travis J.; Zhang, Jing (February 2013).
"Biomarkers of Parkinson's disease: current status and future perspectives" . Drug Discovery Today . 18 (3–4): 155–162.
doi :
10.1016/j.drudis.2012.09.001 .
PMC
3557745 .
PMID
22982303 .
^ Hsiao, Ing-Tsung; Weng, Yi-Hsin; Hsieh, Chia-Ju; Lin, Wey-Yil; Wey, Shiaw-Pyng; Kung, Mei-Ping; Yen, Tzu-Chen; Lu, Chin-Song; Lin, Kun-Ju (1 June 2014). "Correlation of Parkinson Disease Severity and F-DTBZ Positron Emission Tomography". JAMA Neurology . 71 (6): 758–766.
doi :
10.1001/jamaneurol.2014.290 .
PMID
24756323 .
^
"A Trial of 18F-AV-133 Positron Emission Tomography (PET) Imaging to Differentiate Subjects With Parkinson's Disease (PD) From Other Movement Disorders" . Clinical Trials . U.S. National Institutes of Health. Retrieved 20 July 2015 .
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