2-Iodoimipramine, a novel ligand for the serotonin transporter.
Iodoimipramine was synthesized by iodinating imipramine with ICI. Iodoimipramine competitively inhibits [3H]imipramine binding with a KI of 0.52 nM and also inhibits [3H]serotonin transport competitively, suggesting that serotonin, imipramine, and iodoimipramine all bind to the same site on the serotonin transporter. Association of [125I]iodoimipramine to platelet membranes in Na+ requires 20 min to reach equilibrium at 25 degrees and 1.5 hr at 0 degrees. [125I] Iodoimipramine binding at equilibrium is saturable and Na+ dependent, with a KD of 0.58 nM and a Bmax of 1.3 pmol/mg at 25 degrees. Serotonin competitively inhibits [125I]iodoimipramine binding, with a KI of 1.3 microM. [125I]Iodoimipramine bound at 0 degrees in the presence of Na+ does not dissociate unless the temperature is raised or Na+ is removed from the medium. At 25 degrees, dissociation of [125I] iodoimipramine from platelet membranes in the presence of Na+ is only partial, with 40% of the ligand remaining persistently bound over 5 hr after a 50-fold dilution.
Humphreys
C J
CJ
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
Cassel
D
D
Rudnick
G
G
D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007099:Imipramine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D013696:Temperature
D002352:Carrier Proteins; D008024:Ligands; D050486:Serotonin Plasma Membrane Transport Proteins; C061446:2-iodoimipramine; D012701:Serotonin; D007099:Imipramine