Development of new brain imaging agents based upon nocaine-modafinil hybrid monoamine transporter inhibitors

John L. Musachio; Jinsoo Hong; Masanori Ichise; Nicholas Seneca; Amira K. Brown; Jeih San Liow; Christer Halldin; Robert B. Innis; Victor W. Pike; Rong He; Jia Zhou; Alan P. Kozikowski

doi:10.1016/j.bmcl.2006.03.066

Development of new brain imaging agents based upon nocaine-modafinil hybrid monoamine transporter inhibitors

John L. Musachio, Jinsoo Hong, Masanori Ichise, Nicholas Seneca, Amira K. Brown, Jeih San Liow, Christer Halldin, Robert B. Innis, Victor W. Pike, Rong He, Jia Zhou, Alan P. Kozikowski

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

¹¹C-labeled (+)-trans-2-[[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3-yl]methylsu lfanyl]ethanol ([¹¹C]5) and (+)-trans-2-[[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3-yl]methylsu lfanyl]-1-(piperidin-1-yl)ethanone ([¹¹C]6) were synthesized and evaluated as new imaging agents for the norepinephrine transporter (NET). [¹¹C]5 and [¹¹C]6 display high affinity for the NET in vitro (K_i = 0.94 and 0.68 nM, respectively) and significant selectivity over the dopamine (DAT) and serotonin transporters (SERT). Because of their high affinity and favorable transporter selectivities we speculated that these ligands might serve as useful PET agents for imaging NET in vivo. Contrary to our expectations, both of these ligands provided brain images that were more typical of those shown by agents binding to the DAT.

Original language	English (US)
Pages (from-to)	3101-3104
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	12
DOIs	https://doi.org/10.1016/j.bmcl.2006.03.066
State	Published - Jun 15 2006
Externally published	Yes

Keywords

Antidepression
Brain imaging agents
DAT radioligands
Monoamine transporter inhibitors
NET radioligands
PET imaging

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2006.03.066

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Musachio, J. L., Hong, J., Ichise, M., Seneca, N., Brown, A. K., Liow, J. S., Halldin, C., Innis, R. B., Pike, V. W., He, R., Zhou, J., & Kozikowski, A. P. (2006). Development of new brain imaging agents based upon nocaine-modafinil hybrid monoamine transporter inhibitors. Bioorganic and Medicinal Chemistry Letters, 16(12), 3101-3104. https://doi.org/10.1016/j.bmcl.2006.03.066

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title = "Development of new brain imaging agents based upon nocaine-modafinil hybrid monoamine transporter inhibitors",

abstract = "11C-labeled (+)-trans-2-[[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3-yl]methylsu lfanyl]ethanol ([11C]5) and (+)-trans-2-[[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3-yl]methylsu lfanyl]-1-(piperidin-1-yl)ethanone ([11C]6) were synthesized and evaluated as new imaging agents for the norepinephrine transporter (NET). [11C]5 and [11C]6 display high affinity for the NET in vitro (Ki = 0.94 and 0.68 nM, respectively) and significant selectivity over the dopamine (DAT) and serotonin transporters (SERT). Because of their high affinity and favorable transporter selectivities we speculated that these ligands might serve as useful PET agents for imaging NET in vivo. Contrary to our expectations, both of these ligands provided brain images that were more typical of those shown by agents binding to the DAT.",

keywords = "Antidepression, Brain imaging agents, DAT radioligands, Monoamine transporter inhibitors, NET radioligands, PET imaging",

author = "Musachio, {John L.} and Jinsoo Hong and Masanori Ichise and Nicholas Seneca and Brown, {Amira K.} and Liow, {Jeih San} and Christer Halldin and Innis, {Robert B.} and Pike, {Victor W.} and Rong He and Jia Zhou and Kozikowski, {Alan P.}",

note = "Funding Information: We are indebted to the National Institute on Drug Abuse (Grant DA10458) and the NIH/NIMH (Grants 1R41MH070083 and 1R41MH074193) for their support of these studies. This study was also supported by the Intramural Research Program of the National Institutes of Health and National Institute of Mental Health.",

year = "2006",

month = jun,

day = "15",

doi = "10.1016/j.bmcl.2006.03.066",

language = "English (US)",

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pages = "3101--3104",

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T1 - Development of new brain imaging agents based upon nocaine-modafinil hybrid monoamine transporter inhibitors

AU - Musachio, John L.

AU - Hong, Jinsoo

AU - Ichise, Masanori

AU - Seneca, Nicholas

AU - Brown, Amira K.

AU - Liow, Jeih San

AU - Halldin, Christer

AU - Innis, Robert B.

AU - Pike, Victor W.

AU - He, Rong

AU - Zhou, Jia

AU - Kozikowski, Alan P.

N1 - Funding Information: We are indebted to the National Institute on Drug Abuse (Grant DA10458) and the NIH/NIMH (Grants 1R41MH070083 and 1R41MH074193) for their support of these studies. This study was also supported by the Intramural Research Program of the National Institutes of Health and National Institute of Mental Health.

PY - 2006/6/15

Y1 - 2006/6/15

N2 - 11C-labeled (+)-trans-2-[[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3-yl]methylsu lfanyl]ethanol ([11C]5) and (+)-trans-2-[[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3-yl]methylsu lfanyl]-1-(piperidin-1-yl)ethanone ([11C]6) were synthesized and evaluated as new imaging agents for the norepinephrine transporter (NET). [11C]5 and [11C]6 display high affinity for the NET in vitro (Ki = 0.94 and 0.68 nM, respectively) and significant selectivity over the dopamine (DAT) and serotonin transporters (SERT). Because of their high affinity and favorable transporter selectivities we speculated that these ligands might serve as useful PET agents for imaging NET in vivo. Contrary to our expectations, both of these ligands provided brain images that were more typical of those shown by agents binding to the DAT.

AB - 11C-labeled (+)-trans-2-[[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3-yl]methylsu lfanyl]ethanol ([11C]5) and (+)-trans-2-[[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3-yl]methylsu lfanyl]-1-(piperidin-1-yl)ethanone ([11C]6) were synthesized and evaluated as new imaging agents for the norepinephrine transporter (NET). [11C]5 and [11C]6 display high affinity for the NET in vitro (Ki = 0.94 and 0.68 nM, respectively) and significant selectivity over the dopamine (DAT) and serotonin transporters (SERT). Because of their high affinity and favorable transporter selectivities we speculated that these ligands might serve as useful PET agents for imaging NET in vivo. Contrary to our expectations, both of these ligands provided brain images that were more typical of those shown by agents binding to the DAT.

KW - Antidepression

KW - Brain imaging agents

KW - DAT radioligands

KW - Monoamine transporter inhibitors

KW - NET radioligands

KW - PET imaging

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IS - 12

ER -

Development of new brain imaging agents based upon nocaine-modafinil hybrid monoamine transporter inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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