[摘要]：Major depressive disorder is one of the leading causes of disability worldwide. Current treatments for depression mostly target the serotonin (5-HT) signaling pathways because decreased concentrations of 5-HT, a major regulator of mood, sleep, appetite and emotion, in the brain are strongly associated with affective disorders. The most commonly used antidepressants include the tricyclic an selective 5-HT reuptake inhibitors, dual 5-HT and norepinephrine reuptake inhibitors, monoamine oxidase (MAO) inhibitors and, more recently, drugs that target the large family of 5-HT receptors. Lundbeck and Takeda have recently developed a new type of antidepressant, Lu-AA-21004, with a novel mode of action in that it functions as a multitargeted drug affecting multiple 5-HT receptors and the 5-HT transporter to increase synaptic 5-HT concentrations. The drug showed a favorable pharmacokinetic/pharmacodynamic profile in both animals and humans and is currently in phase Ill trials for the treatment of major depressive disorder and generalized anxiety. Preliminary studies show that Lu-AA-21004 has mild side effects and good efficacy in comparison to other drugs used to treat depression. Longer-term studies on safety, tolerability and efficacy in the treatment of affective disorders are currently under way and the drug is due to be registered with U.S. and European agencies within the next year.
