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 journalArticle

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 (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.

Original languageEnglish (US)
Pages (from-to)3101-3104
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number12
DOIs
StatePublished - Jun 15 2006
Externally publishedYes

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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  • Cite this

    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