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 K(d) 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 language||English (US)|
|Number of pages||8|
|State||Published - May 1 1995|
ASJC Scopus subject areas
- Molecular Medicine