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[ 125 I]RTI‐55 Binding to Cocaine‐Sensitive Dopaminergic and Serotonergic Uptake Sites in the Human Brain
Author(s) -
Little Karley Y.,
Kirkman Jacob A.,
Carroll F. Ivy,
Breese George R.,
Duncan Gary E.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb07435.x
Subject(s) - serotonergic , dopaminergic , neuroscience , human brain , chemistry , serotonin , dopamine , pharmacology , biology , biochemistry , receptor
[ 125 I]RTI‐55 is a newly synthesized cocaine congener that may offer advantages over other ligands previously used to examine cocaine binding sites. However, the in vitro pharmacological and anatomical characterization of [ 125 I]RTI‐55 binding sites has not been previously performed in human brain. To determine the specificity, stability, and feasibility of [ 125 I]RTI‐55 for use in radioligand binding assays in postmortem human tissue, a series of experiments were performed characterizing [ 125 I]RTI‐55 binding sites in human brain using homogenized membrane preparations and quantitative autoradtography. Analysis of the association, dissociation, and saturation data favored two‐phase processes. A curve‐fitting analysis of the data derived in saturation experiments found a high‐affinity site with K D = 66 ± 35 p M and S max = 13.2 ± 10.1 pmol/g of tissue and a low‐affinity site with K D = 1.52 ± 0.55 n M and B max of 47.5 ± 11‐2 pmol/g of tissue. Competition by ligands known to bind to the dopamine transporter showed a rank order of RTI‐55 > GBR‐12909 > mazindol > WIN 35428 > = methylphenidate > (−)‐cocaine > buproprion > (±)‐amphetamine. Binding to serotonergic sites was evaluated in the midbrain. Results of the saturation experiment performed autoradiographically in the midbrain showed a single site with K D = 370 ± 84 p M. It appears that [ 125 I]RTI‐55 should be useful in further studies of the regulation of cocaine binding sites using postmortem human specimens.