Selective labeling of the dopamine transporter by the high affinity ligand 3β-(4-[125I]Iodophenyl)tropane-2β-carboxylic acid isopropyl ester

J. W. Boja, J. L. Cadet, T. A. Kopajtic, J. Lever, H. H. Seltzman, C. D. Wyrick, A. H. Lewin, P. Abraham, F. I. Carroll

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70 Scopus citations

Abstract

The iodine-125 analog of the dopaminergically selective cocaine analog 3β-(4-iodophenyl)tropane-2β-carboxylic acid isopropyl ester (RTI-121) was evaluated as a probe for the dopamine transporter in rat striatum. Saturation and kinetic studies indicated that [125I]RTI-121 binds to both high and low affinity components. The Kd of the high affinity component was 0.14 ± 0.01 nM (mean ± standard error), whereas the low affinity component demonstrated an affinity of 1.59 ± 0.09 nM. The corresponding numbers of striatal binding sites labeled by [125I]RTI-121 were 295 ± 6 and 472 ± 59 pmol/g of tissue (original wet weight), respectively, Intrastriatal injections of 6-hydroxydopamine eliminated >90% of specific [125I]RTI-121 binding in the striatum. The pharmacological profile of specific [125I]RTI-121 binding in the rat striatum was consistent with that of the dopamine transporter. There was a strong (r = 0.98, p < 0.0001) correlation between the potencies of drugs that displaced specific [125I]RTI-121 binding and the potencies of these drugs to inhibit the uptake of [3H]dopamine. In contrast, no correlation was found for the potencies of drugs to inhibit the uptake of either [3H]norepinephrine or [3H]serotonin. Autoradiographs produced using [125I]RTI-121 demonstrated a distribution of label consistent with the distribution of dopaminergic neurons in rat brain. Because of its high affinity and high selectivity for the dopamine transporter, [125I]RTI-121 may be an extremely useful ligand for the dopamine transporter.

Original languageEnglish (US)
Pages (from-to)779-786
Number of pages8
JournalMolecular Pharmacology
Volume47
Issue number4
StatePublished - Apr 1995
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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