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Dihydrotetrabenazine

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Dihydrotetrabenazine
DTBZ ambiguous.svg
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
  • 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
C19H29NO3
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).

Dihydrotetrabenazine or DTBZ is an organic compound with the chemical formula C19H29NO3. 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]

Contents

Use in Positron Emission Tomography

Carbon-11 labeled (+)DTBZ(right) and fluorine-18 labeled fluoropropylated (+)DTBZ(left) 11CDTBZ 18FFPDTBZ.svg
Carbon-11 labeled (+)DTBZ(right) and fluorine-18 labeled fluoropropylated (+)DTBZ(left)
Reconstructed data from PET scan of healthy human brain using [18F]Fluoropropyl-DTBZ indicating VMAT2 distribution [2]

[11C]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 [18F]DTBZ has been shown to be well, inversely correlated with the severity of Parkinson's disease. [6]

Avid Radiopharmaceuticals has sponsored clinical trials of [18F]AV-133 (or [18F]Fluoropropyl-(+)-DTBZ) to identify subjects with dopaminergic degeneration. [7]

See also

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ "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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