High affinity binding sites for [³H]imipramine in human brain and platelet: Clinical implications

High affinity and saturable binding sites for [³H]imipramine have been demonstrated in membrane preparations from human brain and platelet. These binding sites appear to be specific for tricyclic antidepressants since specifically bound [³H]imipramine is displaced by pharmacologically-active tricyclic antidepressants at low concentrations. Tertiary amine antidepressants such as imipramine and amitriptyline are more potent inhibitors of [³H]imipramine binding than are the corresponding secondary amines nortriptyline and desipramine; suggesting a relationship between the high affinity binding sites and the serotonin reuptake site. In contrast other psychotropic drugs and neurotransmitter agonists and antagonists have little or no effect on specific [³H]imipramine binding. The characteristics of [³H]Imipramine binding in human brain membranes are very similar (if not identical) to that of human platelets suggesting that the latter may be a useful model in studying the pharmacological significance of these binding sites. Preliminary studies of [³H]imipramine binding in platelets from severely depressed patients reveal a significant (≥ 30%) decrease in binding site density (B_max) when compared to platelets from healthy age-matched controls.