[125I]RTI-55 binding to cocaine-sensitive dopaminergic and serotonergic uptake sites in the human brain

J Neurochem. 1993 Dec;61(6):1996-2006. doi: 10.1111/j.1471-4159.1993.tb07435.x.


[125I]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 [125I]RTI-55 binding sites has not been previously performed in human brain. To determine the specificity, stability, and feasibility of [125I]RTI-55 for use in radioligand binding assays in postmortem human tissue, a series of experiments were performed characterizing [125I]RTI-55 binding sites in human brain using homogenized membrane preparations and quantitative autoradiography. 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 KD = 66 +/- 35 pM and Bmax = 13.2 +/- 10.1 pmol/g of tissue and a low-affinity site with KD = 1.52 +/- 0.55 nM and Bmax 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 > maxindol > 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 KD = 370 +/- 84 pM. It appears that [125I]RTI-55 should be useful in further studies of the regulation of cocaine binding sites using postmortem human specimens.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Autoradiography
  • Binding Sites
  • Binding, Competitive
  • Carrier Proteins / metabolism*
  • Caudate Nucleus / metabolism*
  • Cell Membrane / metabolism
  • Cocaine / analogs & derivatives*
  • Cocaine / metabolism*
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Female
  • Humans
  • Iodine Radioisotopes
  • Kinetics
  • Male
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Proteins*
  • Middle Aged
  • Nerve Tissue Proteins*
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins


  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Iodine Radioisotopes
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
  • Cocaine
  • Dopamine