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N‐substituted phenyltropanes as in vivo binding ligands for rapid imaging studies of the dopamine transporter
Author(s) -
Scheffel Ursula,
Lever John R.,
Abraham Philip,
Parham Karol R.,
Mathews William B.,
Kopajtic Theresa,
Carroll F. Ivy,
Kuhar Michael J.
Publication year - 1997
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199704)25:4<345::aid-syn5>3.0.co;2-a
Subject(s) - dopamine transporter , in vivo , dopamine plasma membrane transport proteins , dopamine , chemistry , striatum , transporter , dopamine uptake inhibitors , pharmacology , biochemistry , stereochemistry , dopaminergic , neuroscience , biology , gene , microbiology and biotechnology
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. Synapse 25:345–349, 1997. © 1997 Wiley‐Liss, Inc.