N-substituted phenyltropanes as in vivo binding ligands for rapid imaging studies of the dopamine transporter

Ursula Scheffel, John R. Lever, Philip Abraham, Karol R. Parham, William B. Mathews, Theresa Kopajtic, F. Ivy Carroll, Michael J. Kuhar

Research output: Contribution to journalArticlepeer-review

Abstract

Variously substituted phenyltropanes are proven as superb binding ligands for the dopamine transporter (DAT). In this study, we examine four N- substituted phenyltropanes which are derivatives of RTI-55 as in vivo binding ligands in mice. In this series, the methyl group on the nitrogen was replaced by a propyl (RTI-310), an allyl (RTI-311), a butyl (RTI-312), or a fluoropropyl (RTI-313) group. The in vitro binding potencies of these compounds at rat striatal DAT varied somewhat but were about 1 nM. While these compounds did not display marked selectivity for the dopamine transporter, they were more selective than RTI-55. Injection of the radiolabeled compound into mice resulted in striatal-to-cerebellar ratios that varied from about 4.5-6.5. The ratios peaked most rapidly for RTI-311 and RTI-313, at about 20 min. Pharmacological inhibition studies indicated that these compounds were binding to DATs in the striatum, as expected. These findings suggest that some compounds of this type may be excellent in vivo binding ligands for rapid imaging studies of the DAT.

Original languageEnglish (US)
Pages (from-to)345-349
Number of pages5
JournalSynapse
Volume25
Issue number4
DOIs
StatePublished - Apr 1997

Keywords

  • cocaine
  • dopamine
  • imaging

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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