Serotonergic and Noradrenergic Neuromodulation in the Hippocampus and the Mechanism of Action of Antidepressants
Despite the recent explosive progress of brain imaging and molecular biology, the pathophysiology of affective disorders and the mechanism of action of antidepressant drugs remain unknown. There is no consensus about the net effect of chronic antidepressant treatment on serotonergic and noradrenergic neurotransmission, particularly noradrenergic neurotransmission. Novel antidepressants, such as selective serotonin (5-HT) reuptake inhibitors (SSRIs) or reversible inhibitors of monoamine oxidase A (RIMAs) have better side-effect profiles and wide clinical indications compared with classical tricyclic antidepressants. SSRIs such as fluoxetine, sertraline, fluvoxamine, paroxetine, and citalopram have little anticholinergic effect and have been proved to be effective not only for depression but also for obsessive-compulsive disorder, panic disorder, and eating disorder. RIMAs do not have the fatal side effect of old irreversible monoamine oxidase inhibitors, the so-called cheese effect, and among RIMAs such as moclobemide, brofaramine, and toloxatone, moclobemide has efficacy against social phobia. The clinical efficacy of these novel antidepressants against major depression, however, is not significantly different from that of classical antidepressants. The clinical choice of an antidepressant for an individual patient remains primarily based on considerations of side effects and safety rather than efficacy (Lecrubier 1993).
KeywordsEating Disorder Pyramidal Neuron Locus Coeruleus Noradrenergic Neurotransmission Chronic Antidepressant Treatment
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