Antidepressants: past, present and future.

Since the discovery of first antidepressants in mid-1950's, the field has been intensively studied. Several new classes of compounds emerged and several hypotheses on the mechanism of their action were proposed. The novel antidepressants are either selective and reversible monoamine oxidase inhibitors, (e.g., moclobemide), or selective serotonin reuptake inhibitors (e.g., citalopram or paroxetine), or serotonin and noradrenaline reuptake inhibitors (e.g. , venlafaxine). Recently neuropeptides (e.g., thyrotropin-releasing hormone,TRH) or antagonists of neuropeptide receptors (e.g., tachykinin NK(1) receptor) undergo clinical tests. Several hypotheses proposed the predominant involvement of one or few neurotransmitter receptors in the mechanism of antidepressant action, but it is now assumed that several distinct receptor mechanisms' trigger different but converging intracellular signal cascades that activate transcription factors, which, in turn, promote the expression of genes encoding for proteins, that play a crucial role in restoring of neuronal functions involved in mood regulation.