Recent studies have provided evidence that structural remodeling of certain brain regions is a feature of depressive illness, and the postulated underlying mechanisms contribute to the idea that there is more to
antidepressant actions that can be explained exclusively by a monoaminergic hypothesis. This review summarizes recent neurobiological studies on the
antidepressant,
tianeptine (S-1574, [3-chloro-6-methyl-5,5-dioxo-6,11-dihydro-(c,f)-dibenzo-(1,2-
thiazepine)-11-yl) amino]-7 heptanoic
acid,
sodium salt), a compound with structural similarities to the
tricyclic antidepressant agents, the efficacy and good tolerance of which have been clearly established. These studies have revealed that the neurobiological properties of
tianeptine involve the dynamic interplay between numerous
neurotransmitter systems, as well as a critical role of structural and functional plasticity in the brain regions that permit the full expression of emotional learning. Although the story is far from complete, the schema underlying the effect of
tianeptine on central plasticity is the most thoroughly studied of any
antidepressants. Effects of
tianeptine on neuronal excitability, neuroprotection, anxiety, and memory have also been found. Together with clinical data on the efficacy of
tianeptine as an
antidepressant, these actions offer insights into how compounds like
tianeptine may be useful in the treatment of neurobiological features of
depressive disorders.