Imipramine binding sites in brain and platelets: role in affective disorders

Specific recognition sites for the tricyclic antidepressant drug [3H]imipramine ([3H]IMI) have been demonstrated in brain and platelets of various species, including human beings, and suggested to play a role in the mode of action of antidepressants and serve as a biological marker in some forms of depression. In brain, [3H]IMI was shown to bind to at least two classes of sites; high- and low-affinity. Only the high-affinity, sodium-dependent binding was found to be associated with the serotonin transporter complex. Decreased density of [3H]IMI sites in platelets of depressed patients was observed in some but not all clinical studies. A reason for this discrepancy could be the recent finding that the sodium-dependent [3H]IMI sites relevant for regulation of serotonin uptake represent only about 70% of the 'specific' [3H]IMI binding defined, as in most assays, by excess desipramine. It is suggested that the sodium-dependent [3H]IMI binding or a more selective ligand (e.g. [3H]paroxetine) should be used in future studies of serotonin transporter function in depression.