Desipramine lowers tritiated para-aminoclonidine binding in platelets of depressed patients.
Platelet adrenergic receptor binding has been studied by several groups of investigators as a possible marker for depression and other psychiatric conditions. Although some of the findings have been discrepant, the results of the majority of studies that have used imidazoline compounds as ligands have confirmed elevated alpha 2-adrenergic receptor binding in depression. We have emphasized the advantages of obtaining platelet-purified plasma membranes and using tritiated para-aminoclonidine as the ligand of choice. By using "site-selective" concentrations of tritiated para-aminoclonidine, we have identified two high-affinity-binding sites of the platelet alpha 2-adrenergic receptor that appear to be upregulated in depression before treatment. Depressed patients were treated with desipramine hydrochloride for 6 to 8 weeks, and platelet binding was reassessed. Desipramine reduced binding to nearly normal levels at both site-selective concentrations of tritiated para-aminoclonidine. The concentrations of plasma catecholamines could play a role in the downregulation of binding at posttreatment. We discuss these findings in the context of platelet imidazoline-binding sites being a possible state-dependent marker for depression.
Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio.
J E
JE
Piletz
A
A
Halaris
A
A
Saran
M R
MR
Marler
D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D015415:Biomarkers; D001792:Blood Platelets / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives* / Q000378:metabolism; D003866:Depressive Disorder / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation; D006801:Humans; D008024:Ligands; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium; D015854:Up-Regulation
D000316:Adrenergic alpha-Agonists; D015415:Biomarkers; D008024:Ligands; D011942:Receptors, Adrenergic, alpha; D014316:Tritium; C016986:apraclonidine; D003000:Clonidine; D003891:Desipramine