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Pathway Description
Fluoxetine - Serotonin reuptake Inhibition Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-07-05
Last Updated: 2023-11-27
Fluoxetine is a selective serotonin reuptake inhibitor that exerts anti-depressive effects by selectively inhibiting serotonin reuptake in the brain. One metabolite of fluoxetine, norfluoxetine (N- desmethyl fluoxetine) is biologically active. Fluoxetine competes for the same binding site as serotonin on the the sodium-dependent serotonin transporter (SLC6A4). This increases the concentrations of serotonin in the synaptic cleft and reverses the state of low concentration seen in depression. Higher concentration of serotonin has also been shown to have long-term neuromodulatory effects. Binding of serotonin to certain serotonin receptors activate adenylate cyclase, which produces cAMP. cAMP activates protein kinase A which activates cAMP-responsive binding protein 1 (CREB-1). CREB-1 enters the nucleus and affects transcription of brain-derived neurotrophic factor (BDNF). BDNF subsequently stimulates neurogenesis, which may contribute to the long-term reversal of depression. The slow elimination and long half life of fluoxetine and its active metabolite differentiates it from other anti-depressants.
References
Fluoxetine - Serotonin reuptake Inhibition pathway References
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Pubmed: 14702039
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