Dihydrotetrabenazine

Dihydrotetrabenazine
Identifiers
CAS Number	3466-75-9;
3D model (JSmol)	Interactive image;
ChemSpider	110379 ;
PubChem CID	123836;
CompTox Dashboard (EPA)	DTXSID90956148 ;
	InChI 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;
	SMILES COC1=C(OC)C=C(C(CC(O)C(CC(C)C)C2)N2CC3)C3=C1;
Properties
Chemical formula	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). Infobox references

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]

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 [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 K_i whereas the levorotary (or (-) isomer) has approximately 1000 fold lower affinity with a K_i 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]

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.

[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.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

Use in Positron Emission Tomography

See also

References