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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 110379
| ChemSpiderID = 110379
| PubChem = 123836
| SMILES = COC1=C(OC)C=C(C(CC(O)C(CC(C)C)C2)N2CC3)C3=C1
| SMILES = COC1=C(OC)C=C(C(CC(O)C(CC(C)C)C2)N2CC3)C3=C1
| 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
| 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
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'''Dihydrotetrabenazine''' or '''DTBZ''' is an [[organic compound]] with the [[chemical formula]] C<sub>19</sub>H<sub>29</sub>NO<sub>3</sub>. 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 [[Positron emission tomography|PET]] radioligands for examining [[VMAT2]].<ref>{{cite journal|last1=Koeppe|first1=RA|last2=Gilman|first2=S|last3=Joshi|first3=A|last4=Liu|first4=S|last5=Little|first5=R|last6=Junck|first6=L|last7=Heumann|first7=M|last8=Frey|first8=KA|last9=Albin|first9=RL|title=11C-DTBZ and 18F-FDG PET measures in differentiating dementias.|journal=Journal of nuclear medicine : official publication, Society of Nuclear Medicine|date=June 2005|volume=46|issue=6|pages=936–44|pmid=15937303}}</ref>
'''Dihydrotetrabenazine''' or '''DTBZ''' is an [[organic compound]] with the [[chemical formula]] C<sub>19</sub>H<sub>29</sub>NO<sub>3</sub>. 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 [[Positron emission tomography|PET]] [[radioligand]]s for examining [[VMAT2]].<ref>{{cite journal|last1=Koeppe|first1=RA|last2=Gilman|first2=S|last3=Joshi|first3=A|last4=Liu|first4=S|last5=Little|first5=R|last6=Junck|first6=L|last7=Heumann|first7=M|last8=Frey|first8=KA|last9=Albin|first9=RL|title=11C-DTBZ and 18F-FDG PET measures in differentiating dementias.|journal=Journal of Nuclear Medicine |date=June 2005|volume=46|issue=6|pages=936–44|pmid=15937303}}</ref>


==Use in Positron Emission Tomography==
==Use in Positron Emission Tomography==
[[File:11CDTBZ 18FFPDTBZ.svg|left|thumb|350px|Carbon-11 labeled (+)DTBZ(right) and fluorine-18 labeled fluoropropylated (+)DTBZ(left)]]
[[File:11CDTBZ 18FFPDTBZ.svg|left|thumb|350px|Carbon-11 labeled (+)DTBZ(right) and fluorine-18 labeled fluoropropylated (+)DTBZ(left)]]
[[File:Brain-Imaging-of-Vesicular-Monoamine-Transporter-Type-2-in-Healthy-Aging-Subjects-by-18F-FP-(+)-pone.0075952.s001.ogv|thumb|left|350px|thumbtime=5|Reconstructed data from PET scan of healthy human brain using [<sup>18</sup>F]Fluoropropyl-DTBZ indicating [[VMAT2]] distribution<ref>{{cite journal|last1=Lin|first1=KJ|last2=Weng|first2=YH|last3=Hsieh|first3=CJ|last4=Lin|first4=WY|last5=Wey|first5=SP|last6=Kung|first6=MP|last7=Yen|first7=TC|last8=Lu|first8=CS|last9=Hsiao|first9=IT|title=Brain imaging of vesicular monoamine transporter type 2 in healthy aging subjects by 18F-FP-(+)-DTBZ PET.|journal=PLOS ONE|date=2013|volume=8|issue=9|pages=e75952|pmid=24098749|accessdate=7 July 2015|doi=10.1371/journal.pone.0075952}}</ref>]] [<sup>11</sup>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]].<ref>{{cite journal|last1=Frey|first1=KA|last2=Koeppe|first2=RA|last3=Kilbourn|first3=MR|last4=Vander Borght|first4=TM|last5=Albin|first5=RL|last6=Gilman|first6=S|last7=Kuhl|first7=DE|title=Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging.|journal=Annals of Neurology|date=December 1996|volume=40|issue=6|pages=873–84|pmid=9007092|accessdate=20 July 2015|doi=10.1002/ana.410400609}}</ref> There are two [[enantiomers]] of alpha-dihydrotetrabenazine, and the [[dextrorotary]](or (+) isomer) has a high [[Ligand (biochemistry)#Receptor.2Fligand binding affinity|affinity]] of about 1 nanomolar K<sub>i</sub> whereas the [[levorotary]] (or (-) isomer) has approximately 1000 fold lower affinity with a K<sub>i</sub> of about 2 micromolar.<ref>{{cite journal|last1=Kilbourn|first1=M|last2=Lee|first2=L|last3=Vander Borght|first3=T|last4=Jewett|first4=D|last5=Frey|first5=K|title=Binding of alpha-dihydrotetrabenazine to the vesicular monoamine transporter is stereospecific.|journal=European Journal of Pharmacology|date=24 May 1995|volume=278|issue=3|pages=249–52|pmid=7589162|accessdate=20 July 2015|doi=10.1016/0014-2999(95)00162-e}}</ref>
[[File:Brain-Imaging-of-Vesicular-Monoamine-Transporter-Type-2-in-Healthy-Aging-Subjects-by-18F-FP-(+)-pone.0075952.s001.ogv|thumb|left|350px|thumbtime=5|Reconstructed data from PET scan of healthy human brain using [<sup>18</sup>F]Fluoropropyl-DTBZ indicating [[VMAT2]] distribution<ref>{{cite journal|last1=Lin|first1=KJ|last2=Weng|first2=YH|last3=Hsieh|first3=CJ|last4=Lin|first4=WY|last5=Wey|first5=SP|last6=Kung|first6=MP|last7=Yen|first7=TC|last8=Lu|first8=CS|last9=Hsiao|first9=IT|title=Brain imaging of vesicular monoamine transporter type 2 in healthy aging subjects by 18F-FP-(+)-DTBZ PET.|journal=PLOS ONE|date=2013|volume=8|issue=9|pages=e75952|pmid=24098749|doi=10.1371/journal.pone.0075952|pmc=3786914|doi-access=free|bibcode=2013PLoSO...875952L }}<!--|access-date=7 July 2015--></ref>]] [<sup>11</sup>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]].<ref>{{cite journal|last1=Frey|first1=KA|last2=Koeppe|first2=RA|last3=Kilbourn|first3=MR|last4=Vander Borght|first4=TM|last5=Albin|first5=RL|last6=Gilman|first6=S|last7=Kuhl|first7=DE|title=Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging.|journal=Annals of Neurology|date=December 1996|volume=40|issue=6|pages=873–84|pmid=9007092|doi=10.1002/ana.410400609|url=https://deepblue.lib.umich.edu/bitstream/2027.42/50362/1/410400609_ftp.pdf|hdl=2027.42/50362|s2cid=9419161|hdl-access=free}}<!--|access-date=20 July 2015--></ref> There are two [[enantiomers]] of alpha-dihydrotetrabenazine, and the [[dextrorotary]](or (+) isomer) has a high [[Ligand (biochemistry)#Receptor.2Fligand binding affinity|affinity]] of about 1 nanomolar K<sub>i</sub> whereas the [[levorotary]] (or (-) isomer) has approximately 1000 fold lower affinity with a K<sub>i</sub> of about 2 micromolar.<ref>{{cite journal|last1=Kilbourn|first1=M|last2=Lee|first2=L|last3=Vander Borght|first3=T|last4=Jewett|first4=D|last5=Frey|first5=K|title=Binding of alpha-dihydrotetrabenazine to the vesicular monoamine transporter is stereospecific.|journal=European Journal of Pharmacology|date=24 May 1995|volume=278|issue=3|pages=249–52|pmid=7589162|doi=10.1016/0014-2999(95)00162-e}}<!--|access-date=20 July 2015--></ref>


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.<ref>{{cite journal|last1=Wang|first1=Jian|last2=Hoekstra|first2=Jake G.|last3=Zuo|first3=Chuantao|last4=Cook|first4=Travis J.|last5=Zhang|first5=Jing|title=Biomarkers of Parkinson's disease: current status and future perspectives|journal=Drug Discovery Today|date=February 2013|volume=18|issue=3-4|pages=155–162|doi=10.1016/j.drudis.2012.09.001}}</ref> Moreover, the VMAT2 density as determined by [<sup>18</sup>F]DTBZ has been shown to be well, inversely correlated with the severity of [[Parkinson's disease]].<ref>{{cite journal|last1=Hsiao|first1=Ing-Tsung|last2=Weng|first2=Yi-Hsin|last3=Hsieh|first3=Chia-Ju|last4=Lin|first4=Wey-Yil|last5=Wey|first5=Shiaw-Pyng|last6=Kung|first6=Mei-Ping|last7=Yen|first7=Tzu-Chen|last8=Lu|first8=Chin-Song|last9=Lin|first9=Kun-Ju|title=Correlation of Parkinson Disease Severity and F-DTBZ Positron Emission Tomography|journal=JAMA Neurology|date=1 June 2014|volume=71|issue=6|pages=758|doi=10.1001/jamaneurol.2014.290}}</ref>
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.<ref>{{cite journal|last1=Wang|first1=Jian|last2=Hoekstra|first2=Jake G.|last3=Zuo|first3=Chuantao|last4=Cook|first4=Travis J.|last5=Zhang|first5=Jing|title=Biomarkers of Parkinson's disease: current status and future perspectives|journal=Drug Discovery Today|date=February 2013|volume=18|issue=3–4|pages=155–162|doi=10.1016/j.drudis.2012.09.001|pmc=3557745|pmid=22982303}}</ref> Moreover, the VMAT2 density as determined by [<sup>18</sup>F]DTBZ has been shown to be well, inversely correlated with the severity of [[Parkinson's disease]].<ref>{{cite journal|last1=Hsiao|first1=Ing-Tsung|last2=Weng|first2=Yi-Hsin|last3=Hsieh|first3=Chia-Ju|last4=Lin|first4=Wey-Yil|last5=Wey|first5=Shiaw-Pyng|last6=Kung|first6=Mei-Ping|last7=Yen|first7=Tzu-Chen|last8=Lu|first8=Chin-Song|last9=Lin|first9=Kun-Ju|title=Correlation of Parkinson Disease Severity and F-DTBZ Positron Emission Tomography|journal=JAMA Neurology|date=1 June 2014|volume=71|issue=6|pages=758–766|doi=10.1001/jamaneurol.2014.290|pmid=24756323|doi-access=}}</ref>


[[Avid Radiopharmaceuticals]] is sponsoring clinical trials of [<sup>18</sup>F]AV-133 (or [<sup>18</sup>F]Fluoropropyl-(+)-DTBZ) to identify subjects with dopaminergic degeneration.<ref>{{cite web|title=A Trial of 18F-AV-133 Positron Emission Tomography (PET) Imaging to Differentiate Subjects With Parkinson's Disease (PD) From Other Movement Disorders|url=https://clinicaltrials.gov/ct2/show/NCT01550484|website=Clinical Trials|publisher=U.S. National Institutes of Health|accessdate=20 July 2015}}</ref>
[[Avid Radiopharmaceuticals]] has sponsored clinical trials of [<sup>18</sup>F]AV-133 (or [<sup>18</sup>F]Fluoropropyl-(+)-DTBZ) to identify subjects with dopaminergic degeneration.<ref>{{cite web|title=A Trial of 18F-AV-133 Positron Emission Tomography (PET) Imaging to Differentiate Subjects With Parkinson's Disease (PD) From Other Movement Disorders|url=https://clinicaltrials.gov/ct2/show/NCT01550484|website=Clinical Trials|publisher=U.S. National Institutes of Health|access-date=20 July 2015}}</ref>


==See also==
==See also==
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{{Reflist}}
{{Reflist}}


[[Category:VMAT inhibitors]]
{{Monoamine reuptake inhibitors}}

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[[Category:Phenol ethers]]
[[Category:Articles containing video clips]]
[[Category:Articles containing video clips]]
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[[Category:Catechol ethers]]
[[Category:Monoamine-depleting agents]]
[[Category:University of Michigan]]
[[Category:University of Michigan]]
[[Category:VMAT inhibitors]]

Latest revision as of 22:58, 10 March 2024

Dihydrotetrabenazine
Identifiers
3D model (JSmol)
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
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]

Use in Positron Emission Tomography

[edit]
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

[edit]

References

[edit]
  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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