Comparative Affinity of Duloxetine and Venlafaxine for Serotonin and Norepinephrine Transporters in vitro and in vivo, Human Serotonin Receptor Subtypes, and Other Neuronal Receptors

Bymaster, Frank P.; Dreshfield-Ahmad, Laura J.; Threlkeld, Penny G.; Shaw, Janice; Thompson, Linda; Nelson, David L.; Hemrick‐Luecke, Susan K.; Wong, David T.

doi:10.1016/s0893-133x(01)00298-6

Cited by 655 publications

(321 citation statements)

References 30 publications

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“…Serotonin neuronal pathways are involved in the mechanism of action of antidepressant medications and there is considerable evidence that they are involved in the pathogenesis of depression (65)(66)(67). The functional role of 5-HT in the immune system has come under increasing investigation as neuroscientists and immunologists have begun to study the underlying biology that is common to the central nervous system and the immune system (68,69).…”

Section: Discussionmentioning

confidence: 99%

Selective Serotonin Reuptake Inhibitor and Substance P Antagonist Enhancement of Natural Killer Cell Innate Immunity in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

Evans

Lynch

Benton

et al. 2008

Biological Psychiatry

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Background-Natural killer (NK) cells play an important role in innate immunity and are involved in the host defense against human immunodeficiency virus (HIV) infection. This study examines the potential role of three underlying regulatory systems that have been under investigation in central nervous system research as well as immune and viral research: serotonin, neurokinin, and glucocorticoid systems.

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Section: Discussionmentioning

confidence: 99%

Selective Serotonin Reuptake Inhibitor and Substance P Antagonist Enhancement of Natural Killer Cell Innate Immunity in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

Evans

Lynch

Benton

et al. 2008

Biological Psychiatry

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“…These results are similar to in vitro and in vivo studies that showed that systemic administration of duloxetine resulted in penetration into the brain and inhibition of NET. 6,10 Administration of tyramine demonstrated the functional effect of impaired NE reuptake. The administration of duloxetine resulted in a linear dose-dependent increase in the amount of tyramine required to cause an increase of 30 mm Hg systolic blood pressure (PD 30 ) from 120 mg/d.…”

Section: Discussionmentioning

confidence: 99%

“…Ex vivo binding of [ 3 H]-nisoxetine to the NE transporters was evaluated as previously described by Bymaster et al 6 All assays were performed in triplicate. Nonspecific binding was determined by including 10 mol/L desipramine.…”

Section: Ex Vivo Bindingmentioning

confidence: 99%

Clinical Assessment of Norepinephrine Transporter Blockade Through Biochemical and Pharmacological Profiles

et al. 2004

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Background-To assess the sensitivity of biochemical, physiological, and pharmacological markers of peripheral norepinephrine (NE) transporter (NET) function, we chronically antagonized NET by a range of doses of duloxetine [(ϩ)-N-methyl-3-(1-naphthalenyloxy)-2 thiophenepropanamine], which blocks the NE reuptake process. Methods and Results-Duloxetine was administered in a randomized, placebo-controlled study in 15 healthy volunteers.Plasma from duloxetine-treated subjects (ex vivo effect) dose-dependently decreased radioligand binding to human NET (maximum inhibition was 60%) (Pϭ0.02). The dose of intravenous tyramine required to raise systolic blood pressure by 30 mm Hg (PD 30 ) increased dose-dependently with duloxetine and was significant at the end of the 120-mg/d dosage (PϽ0.001). The plasma dihydoxyphenylglycol to NE (DHPG/NE) ratio was reduced significantly at 2 weeks of treatment with 80 mg/d duloxetine (11.3 at baseline, 3.4 at 240 mg/d, PϽ0.001). Plasma NE was significantly increased starting at 120 mg/d duloxetine. Urine results (corrected for 24-hour creatinine excretion) showed a dose-dependent change from the baseline urinary excretion for NE, DHPG, and the DHPG/NE ratio. The most sensitive measure, the DHPG/NE ratio, was significant at the 80-mg dose. Urinary NE excretion was significantly raised after 2 weeks of treatment with 80 mg/d duloxetine (PϽ0.001), the lowest dose used in the study. Conclusions-These findings suggest that the degree of NET blockade can be assessed with the plasma or urine DHPG/NE ratio and the pressor effect of tyramine. Also, the DHPG/NE ratio is more sensitive at the lower end of NET inhibition, whereas tyramine exhibits a linear relation, with NET inhibition commencing at a higher dose.

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“…Duloxetine hydrochloride, a potent serotonin (5-HT) and norepinephrine reuptake inhibitor (8), has been approved for the management of diabetic peripheral neuropathic pain (DPNP) and for the treatment of major depressive disorder. In all three placebo-controlled trials conducted in patients with DPNP, duloxetine demonstrated efficacy in reducing pain severity in patients with DPNP at 60 mg once daily and twice daily (9 -11).…”

mentioning

confidence: 99%

Impact of Disease Characteristics on the Efficacy of Duloxetine in Diabetic Peripheral Neuropathic Pain

et al. 2007

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OBJECTIVE -To evaluate the impact of baseline disease variables related to diabetes and diabetic neuropathy severity on efficacy and safety of duloxetine in the management of diabetic peripheral neuropathic pain.RESEARCH DESIGN AND METHODS -The impact of baseline conditions was evaluated using the data from three pooled placebo-controlled studies for combined duloxetine, doses of 60 mg q.d. and 60 mg b.i.d., versus placebo. The primary efficacy measure was the weekly mean of 24-h average pain severity, and night pain was the secondary measure. Safety and tolerability were assessed.RESULTS -There were no significant (P Ͼ 0.10) interactions of treatment by age (Ͻ65 or Ն65 years), type of diabetes (type 1 or type 2), duration of diabetes (median split Ͻ9.18 or Ն9.18 years), duration of diabetic neuropathy (Ͻ2, 2 to Ͻ6, or Ն6 years), severity of diabetic neuropathy (baseline Michigan Neuropathy Screening Instrument score Ͻ5 or Ն5), baseline A1C level (median split Ͻ7.6 or Ն7.6%), or baseline insulin use (yes/no). Significant interactions for both pain measures were observed in baseline pain subgroups (Brief Pain Inventory average pain, Ն6 and Ͻ6). Duloxetine was more effective in the subgroup with more pain. No significant association was found between any other subgroups (P Ͼ 0.10). Significant interactions (P Ͻ 0.1) occurred with treatment-emergent adverse events when stratified by subgroups.CONCLUSIONS -Pain severity but not variables related to diabetes or neuropathy may predict the effects of duloxetine in diabetic peripheral neuropathic pain. The efficacy of duloxetine is related to the initial pain severity and is generalizable across a broad spectrum of diabetic patients, including those with the highest severity of diabetes or neuropathy. Diabetes Care 30:664 -669, 2007

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Comparative Affinity of Duloxetine and Venlafaxine for Serotonin and Norepinephrine Transporters in vitro and in vivo, Human Serotonin Receptor Subtypes, and Other Neuronal Receptors

Abstract: The blockade of serotonin (5-HT) and norepinephrine (NE) transporters in vitro and in vivo by the dual 5-HT

Cited by 655 publications

References 30 publications

Selective Serotonin Reuptake Inhibitor and Substance P Antagonist Enhancement of Natural Killer Cell Innate Immunity in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

Selective Serotonin Reuptake Inhibitor and Substance P Antagonist Enhancement of Natural Killer Cell Innate Immunity in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

Clinical Assessment of Norepinephrine Transporter Blockade Through Biochemical and Pharmacological Profiles

Impact of Disease Characteristics on the Efficacy of Duloxetine in Diabetic Peripheral Neuropathic Pain

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