Preclinical discovery of duloxetine for the treatment of depression.
BACKGROUND
Affective disorders, including major depressive disorder (MDD), are among the most severely disabling mental disorders, and in many cases are associated with poor treatment outcomes. From the emergence of the monoamine hypothesis of depression, the first-line treatment for MDD had mainly acted by inhibiting monoamine reuptake, and thereby increasing these levels in the synaptic cleft. However, in recent years, several new antidepressant drugs have appeared, including duloxetine, a dual serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor recommended for the treatment of MDD.


METHODS
The article reviews and discusses the biochemical and functional profile of duloxetine splitting the review into acute and long-term treatment with this dual monoamine reuptake inhibitor. In addition, the authors summarize available preclinical behavioral research data, which have demonstrated among other effects, the antidepressant-like activity of duloxetine in several animal models. The authors focus on the most recent literature on synaptic neuroplasticity modulation of this antidepressant drug. Finally, the authors briefly mention other approved indications of duloxetine.


CONCLUSIONS
Duloxetine inhibits 5-HT and NA reuptake, effectively desensitizes various autoreceptors and promotes neuroplasticity. Clinically, duloxetine is an effective antidepressant that is well tolerated and has significant efficacy in the treatment of MDD.
Neuropsychopharmacology Research Group, University of Cadiz, Cadiz, Spain.
Sonia
S
Torres-Sanchez
Laura
L
Perez-Caballero
Juan Antonio
JA
Mico
Julian
J
Elorza
Esther
E
Berrocoso
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D000068736:Duloxetine Hydrochloride; D006801:Humans; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use*
D000928:Antidepressive Agents; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride