Duloxetine Pharmacology: Profile of a Dual Monoamine Modulator

Abstract

Dysregulation within central monoaminergic systems is believed to underlie the pathology of depression. Drugs that selectively inhibit the reuptake of central monoamines have been used clinically to alleviate symptoms of depressive illnesses. Duloxetine, a novel compound currently under investigation for the treatment of depression, binds selectively with high affinity to both norepinephrine (NE) and serotonin (5-HT) transporters and lacks affinity for monoamine receptors within the central nervous system. It has been suggested that dual inhibition of monoamine reuptake processes may offer advantages over other antidepressants currently in use.In preclinical studies, duloxetine mimics many physiologic effects of antidepressants. Consistent with other antidepressants, duloxetine, by acute administration, elevates extracellular monoamine levels, while by chronic administration it does not alter basal monoamine levels. Like the selective serotonin reuptake inhibitor, fluoxetine, by microiontophoretic application, duloxetine inhibits neuronal cell firing. However, in comparison with fluoxetine, duloxetine is a more potent serotonin reuptake inhibitor. Furthermore, in behavioral experiments, duloxetine attenuates immobility in forced swim tests in animal models of depression to a greater extent than several other commonly used antidepressants.In a six-week open label uncontrolled study, duloxetine was evaluated in patients with a history of depression. Duloxetine was effective in treating depression as determined by marked reduction in Hamilton Depression Rating scores. Adverse effects reported during 361

Chronic treatment with duloxetine is necessary for an anxiolytic-like response in the mouse zero maze: the role of the serotonin transporter

“…By contrast, reboxetine had no effect on SERT density, but did significantly reduce NET density in the hippocampus as reported previously . Although the lack of effect of duloxetine on the NET may seem surprising, it is unclear if this drug is truly an SNRI (Karpa et al 2002). In vitro functional experiments using cortical or hippocampal tissue preparations show that duloxetine is more potent at inhibiting [ 3 H]5-HT than [ 3 H]NE reuptake, consistent with selective binding affinity for the SERT over the NET (Karpa et al 2002;Wong et al 1993), but inconsistent with ex vivo binding data showing no selectivity (Kasamo et al 1996).…”

The clinical efficiency of acupuncture in preventing migraine attacks and its effect on serotonin levels

“…[20] In another study the use of antidepressants in the treatment of chronic migraine was not associated with changes in serotonin levels, but it has been shown to be more effective in the management of acute pain. [21] To date there is no such data for venlafaxine.…”

Duloxetine for Patients with Diabetic Peripheral Neuropathic Pain: A 6-Month Open-Label Safety Study

“…Duloxetine hydrochloride (duloxetine) has been shown in preclinical studies to be a selective, balanced, and potent inhibitor of reuptake of both 5-HT and NE [15,16]. In clinical trials, duloxetine administered at doses ranging from 40 to A 120 mg daily has been shown to be safe and effective in the treatment of major depression [17][18][19][20][21].…”