title: Fluoxetine: a case history of its discovery and preclinical development.
abstract: BACKGROUND
  Depression is a multifactorial mood disorder with a high prevalence worldwide. Until now, treatments for depression have focused on the inhibition of monoaminergic reuptake sites, which augment the bioavailability of monoamines in the CNS. Advances in drug discovery have widened the therapeutic options with the synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine.
  
  
  METHODS
  The aim of this case history is to describe and discuss the pharmacokinetic and pharmacodynamic profiles of fluoxetine, including its acute effects and the adaptive changes induced after long-term treatment. Furthermore, the authors review the effect of fluoxetine on neuroplasticity and adult neurogenesis. In addition, the article summarises the preclinical behavioural data available on fluoxetine's effects on depressive-like behaviour, anxiety and cognition as well as its effects on other diseases. Finally, the article describes the seminal studies validating the antidepressant effects of fluoxetine.
  
  
  CONCLUSIONS
  Fluoxetine is the first selective SSRI that has a recognised clinical efficacy and safety profile. Since its discovery, other molecules that mimic its mechanism of action have been developed, commencing a new age in the treatment of depression. Fluoxetine has also demonstrated utility in the treatment of other disorders for which its prescription has now been approved.
authors.affiliation: University of Cadiz, Department of Neuroscience, Neuropsychopharmacology and Psychobiology Research Group , Cádiz 11003 , Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Perez-Caballero
authors.forename: Sonia
authors.initials: S
authors.lastname: Torres-Sanchez
authors.forename: Lidia
authors.initials: L
authors.lastname: Bravo
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Mico
authors.forename: Esther
authors.initials: E
authors.lastname: Berrocoso
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D055808:Drug Discovery / Q000266:history*; D004353:Drug Evaluation, Preclinical / Q000266:history; D005473:Fluoxetine / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D049673:History, 20th Century; D006801:Humans
chemical_list: D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine