Synthesis and biological evaluation of [11C]talopram and [11C]talsupram: candidate PET ligands for the norepinephrine transporter.
PET and SPECT ligands for the norepinephrine transporter (NET) will be important tools for studying the physiology, pathophysiology and pharmacology of the CNS noradrenergic system in vivo. A series of candidate NET ligands were synthesized and characterized in terms of their affinity for human monoamine transporters. The two most promising compounds, talopram and talsupram, were radiolabeled with carbon-11 and evaluated through biodistribution studies in rats and PET imaging studies in a rhesus monkey. Although both compounds displayed high affinity and selectivity for the human NET in vitro, these compounds did not enter the CNS in adequate amounts to be used in PET imaging studies.
McConathy
Jonathan
J
Department of Psychiatry, Emory University, Atlanta, GA 30322, USA.
Owens
Michael J
MJ
Kilts
Clinton D
CD
Malveaux
Eugene J
EJ
Camp
Vernon M
VM
Votaw
John R
JR
Nemeroff
Charles B
CB
Goodman
Mark M
MM
D000478:Alkylation; D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D050483:Dopamine Plasma Membrane Transport Proteins; D007202:Indicators and Reagents; D008024:Ligands; D008253:Macaca mulatta; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins; D049268:Positron-Emission Tomography; D011437:Propylamines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D027981:Symporters / Q000378:metabolism*; D013876:Thiophenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution
D001572:Benzofurans; D050483:Dopamine Plasma Membrane Transport Proteins; D007202:Indicators and Reagents; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011437:Propylamines; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters; D013876:Thiophenes; C496684:talopram; C001750:talsupram