Fluoxetine: a clinically effective non-tricyclic antidepressant

  • Louis Lemberger
  • Ray Fuller
  • David Wong
  • Paul Stark

Abstract

Fluoxetine is a potent inhibitor of the neuronal uptake of serotonin (5-HT). The reuptake of 5-HT into the brain neuron from which it was released is thought to be the major means of removing 5-HT from the synaptic cleft, thereby terminating its action on synaptic receptors. Inhibition of this reuptake increases the concentration of 5-HT in the synaptic cleft and enhances the stimulation of presynaptic and postsynaptic receptors. A consequence of stimulating the presynaptic autoreceptor is a reduced rate of firing of 5-HT neurons and a reduction in 5-HT synthesis and release. Several consequences of stimulating postsynaptic receptors innervated by 5-HT neurons in various brain regions have been identified after fluoxetine administration. In laboratory animals these include activation of neuroendocrine secretion (e.g., corticosterone and prolactin when fluoxetine is combined with 5-hydroxytryptophan), reduction of food intake, alterations in sleep and behavior, enhancement of the analgesic action of morphine, and others. In humans, fluoxetine selectively inhibits the uptake of 5-HT into platelets and presumably in the neurons of the CNS.

Keywords

Morphine Serotonin Histamine Prolactin Clonidine 

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Copyright information

© The contributors 1983

Authors and Affiliations

  • Louis Lemberger
    • 1
  • Ray Fuller
    • 1
  • David Wong
    • 1
  • Paul Stark
    • 1
  1. 1.Lilly Research Laboratories, Eli Lilly and Company, and the Departments of Pharmacology, Medicine, and PsychiatryIndiana University School of MedicineIndianapolisUSA

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