Call for Papers  

Article Details

Serotonin 5-HT<sub>4</sub> Receptors: A New Strategy for Developing Fast Acting Antidepressants?

[ Vol. 20 , Issue. 23 ]


Rebeca Vidal, Elena Castro, Fuencisla Pilar-Cuellar, Jesus Pascual-Brazo, Alvaro Diaz, María Luisa Rojo, Raquel Linge, Alicia Martin, Elsa M. Valdizan and Angel Pazos   Pages 3751 - 3762 ( 12 )


The regulation of the activity of brain monoaminergic systems has been the focus of attention of many studies since the first antidepressant drug emerged 50 years ago. The search for novel antidepressants is deeply linked to the search for fast-acting strategies, taking into account that 2-4 weeks of treatment with classical antidepressant are required before clinical remission of the symptoms becomes evident. In the recent years several hypotheses have been proposed on the basis of the existence of alterations in brain synaptic plasticity in major depression. Recent evidences support a role for 5-HT4 receptors in the pathogenesis of depression as well as in the mechanism of action of antidepressant drugs. In fact, chronic treatment with antidepressant drugs appears to modulate, at different levels, the signaling pathway associated to 5-HT4 receptors, as well as their levels of expression in the brain. Moreover, several experimental studies have identified this receptor subtype as a promising new target for fast-acting antidepressant strategy: the administration of partial agonists of this receptor induces a number of responses similar to those observed after chronic treatment with classical antidepressants, but with a rapid onset of action. They include efficacy in behavioral models of depression, rapid desensitization of 5-HT1A autoreceptors, and modifications in the expression of several molecular markers of brain neuroplasticity.

Although much work remains to be done in order to clarify the real therapeutic potential of these drugs, the evidences reviewed below support the hypothesis that 5-HT4 receptor partial agonists could behave as rapid and effective antidepressants.


5-HT<sub>4</sub> receptors, antidepressants, short term treatment, neuroplasticity.


, , , , , , , , , Department of Physiology and Pharmacology, School of Medicine, Cardenal Herrera Oria s/n, University of Cantabria, 39011 Santander, Spain.

Read Full-Text article