title: Synthesis and evaluation of radiolabeled analogs of the antidepressant drug zimelidine as potential SPECT-ligands for the serotonin transporter.
abstract: Z-3-(4-bromophenyl)-N,N-dimethyl-3-(3-pyridinyl)-2-propen-1-amine or zimelidine (ZIM) and its first metabolite nor-zimelidine, were radioiodinated via a nonisotopic exchange, using the Cu(I)-assisted nucleophilic labeling method. To evaluate their potential as SPECT ligands for the serotonin transporter (SERT), the biodistribution of both ligands was determined and pretreatment "blocking" studies performed. Both radioligands demonstrated a good brain penetration of 0.8-1% ID/g, stable after 60 min., p.i., and a brain/blood ratio of up to 3. In vivo brain distribution did not reveal specific binding. Blocking studies by pretreatment with a known SERT ligand, had minor influence on the uptake of [(123)I]I-ZIM, between the several isolated brain regions. It may therefore be concluded that [(123)I]I-ZIM and [(123)I]I-nor-ZIM do not appear to be promising SPECT ligands for the SERT.
authors.affiliation: Radionuclide Center, Vrije Universiteit, de Boelelaan 1085c, 1081 HV Amsterdam, The Netherlands. jeersels@rnc.vu.nl
authors.forename: Jos L H
authors.initials: JL
authors.lastname: Eersels
authors.forename: Rob P
authors.initials: RP
authors.lastname: Klok
authors.forename: Joost
authors.initials: J
authors.lastname: Verbeek
authors.forename: Allard J
authors.initials: AJ
authors.lastname: Jonker
authors.forename: Jacobus D M
authors.initials: JD
authors.lastname: Herscheid
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009928:Organ Specificity; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D011920:Rats, Inbred WF; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D050486:Serotonin Plasma Membrane Transport Proteins; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D015031:Zimeldine / Q000138:chemical synthesis / Q000493:pharmacokinetics*
chemical_list: D000928:Antidepressive Agents; D007457:Iodine Radioisotopes; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D015031:Zimeldine