Synthesis and biological evaluation of trans-3-phenyl-1-indanamines as potential norepinephrine transporter imaging agents.
The development of radioligands suitable for studying the central nervous system (CNS) norepinephrine transporter (NET) in vivo will provide important new tools for examining the pathophysiology and pharmacotherapy of a variety of neuropsychiatric disorders including major depression. Towards this end, a series of trans-3-phenyl-1-indanamine derivatives were prepared and evaluated in vitro. The biological properties of the most promising compound, [(11)C]3-BrPA, were investigated in rat biodistribution and nonhuman primate PET studies. Despite high in vitro affinity for the human NET, the uptake of [(11)C]3-BrPA in the brain and the heart was not displaceable with pharmacological doses of NET antagonists.
McConathy
Jonathan
J
Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30322, USA.
Owens
Michael J
MJ
Kilts
Clinton D
CD
Malveaux
Eugene J
EJ
Votaw
John R
JR
Nemeroff
Charles B
CB
Goodman
Mark M
MM
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D007189:Indans / Q000138:chemical synthesis*; D008024:Ligands; D008253:Macaca mulatta; D008297:Male; D008657:Metabolic Clearance Rate; D009638:Norepinephrine / Q000378:metabolism; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013045:Species Specificity; D014055:Tomography, Emission-Computed / Q000379:methods
D007189:Indans; D008024:Ligands; D019275:Radiopharmaceuticals; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine