Clinical evidence for serotonin and norepinephrine reuptake inhibition of duloxetine.

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Trivedi MH, Desaiah D, Ossanna MJ, Pritchett YL, Brannan SK, Detke MJ

Clinical evidence for serotonin and norepinephrine reuptake inhibition of duloxetine.

Int Clin Psychopharmacol. 2008 May;23(3):161-9. doi: 10.1097/YIC.0b013e3282f41d7e.

PubMed ID

18408530 [ View in PubMed

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Abstract

Most antidepressants in clinical use are believed to function by enhancing neurotransmission of serotonin [5-hydroxytryptamine (5-HT)] and/or norepinephrine (NE) via inhibition of neurotransmitter reuptake. Agents that affect reuptake of both 5-HT and NE (serotonin-norepinephrine reuptake inhibitors) have been postulated to offer greater efficacy for the treatment of major depressive disorder (MDD). These dual-acting agents also display a broader spectrum of action, including efficacy for MDD and associated painful physical symptoms, diabetic peripheral neuropathic pain, generalized anxiety disorder, and fibromyalgia syndrome. Substantial preclinical evidence shows that duloxetine, an approved drug for the treatment of MDD, generalized anxiety disorder, and the management of diabetic peripheral neuropathic pain, inhibits reuptake of both 5-HT and NE. This paper reviews clinical and neurochemical evidence of duloxetine's effects on 5-HT and NE reuptake inhibition. The clinical evidence supporting duloxetine's effects on NE reuptake inhibition includes indirect measures such as altered excretion of NE metabolites, cardiovascular effects, and treatment-emergent adverse event profiles similar to those for other drugs believed to act through the inhibition of NE reuptake. In summary, the data presented in this report provide clinical evidence of a mechanism for duloxetine involving both 5-HT and NE reuptake inhibition in humans and are consistent with preclinical evidence for 5-HT/NE reuptake inhibition.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Duloxetine	Sodium-dependent noradrenaline transporter	Protein	Humans	Yes	Inhibitor	Details
Duloxetine	Sodium-dependent serotonin transporter	Protein	Humans	Yes	Inhibitor	Details