The effects of reboxetine, a noradrenaline reuptake inhibitor, on the plasma noradrenaline response to a cold pressor test in healthy volunteers

Kelly, Carmel; McAree, S.; Cooper, Stephen; Stevenson, Michael R.

doi:10.1177/026988110201600407

Cited by 6 publications

(6 citation statements)

References 26 publications

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“…Similarly, amphetamine-induced cortisol release was attenuated by atomoxetine treatment. Consistent with our findings, in a recent study, 3 days of reboxetine treatment, an inhibitor of norepinephrine transporter, attenuated the plasma norepinephrine response to a cold pressor test without changing the baseline plasma norepinephrine levels (19). Altogether, these findings suggest that treatment with norepinephrine transporter inhibitors may decrease endocrine responses mediated by central noradrenergic receptors.…”

Section: Discussionsupporting

confidence: 92%

Atomoxetine Attenuates Dextroamphetamine Effects in Humans

Sofuoglu

Poling

Hill

et al. 2009

The American Journal of Drug and Alcohol Abuse

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Section: Discussionsupporting

confidence: 92%

Atomoxetine Attenuates Dextroamphetamine Effects in Humans

Sofuoglu

Poling

Hill

et al. 2009

The American Journal of Drug and Alcohol Abuse

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“…Although some inconsistencies exist about the relationship between heart rate and RPE (4), it is possible that there are no changes in heart frequencies as individuals based their work intensity on their self-perceived heart rate. Blood pressure was not influenced by acute NE reuptake inhibition, a finding that was also observed by Kelly et al (14) and Szabadi et al (34). Despite the significantly lower power outputs in both the normal and warm trial with increased NE reuptake inhibition, there were no differences in the subjects' feelings of perceived exertion.…”

Section: Discussionsupporting

confidence: 84%

“…Rebox, which has a potent NE activity, has already been shown to exert both peripheral and central effects (25,34), and the relationship between both activities is very complex and for the moment unclear (14). In the present study, NE reuptake inhibition increased heart rate at rest in both normal and warm environmental temperatures, an effect that was also observed by Fava et al (6), Mucci (20), and Schüle et al (32).…”

Section: Discussionsupporting

confidence: 80%

“…NE reuptake inhibition has been investigated during exercise in thermoneutral environments, using Rebox (25). Rebox is widely prescribed as an antidepressant (35); it occupies the NE transporter (NET; 14), thereby increasing the concentration of NE in the synaptic cleft (14), and has little or no affinity for the DA and 5-HT uptake sites or for muscarinic H 1 -histaminergic or adrenergic receptors (2). Piacentini and colleagues (25) found that subjects were slower after NE reuptake inhibition and that the hormonal alterations observed indicated a central effect of the drug due to an increase in NE extracellular concentrations (25).…”

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confidence: 99%

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Acute norepinephrine reuptake inhibition decreases performance in normal and high ambient temperature

Roelands¹,

Goekint²,

Heyman³

et al. 2008

Journal of Applied Physiology

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Combined inhibition of dopamine (DA)/norepinephrine (NE) reuptake improves exercise performance and increases core temperature in the heat. A recent study demonstrated that this effect may primarily be related to increased DA activity. NE reuptake inhibition (NERI), however, has received little attention in humans, certainly in the heat, where central fatigue appears to be a main factor influencing performance. Therefore the present study examines the effect of NERI (reboxetine) on exercise capacity, thermoregulation, and hormonal response in normal and high temperature. Nine healthy well-trained male cyclists participated in this study. Subjects ingested either placebo (Pla; 2 x 8 mg) or reboxetine (Rebox; 2 x 8 mg). Subjects exercised in temperate (18 degrees C) or warm (30 degrees C) conditions and cycled for 60 min at 55% W(max) immediately followed by a time trial (TT; Pla18/Rebox18; Pla30/Rebox30) to measure exercise performance. Acute NERI decreased power output and consequently exercise performance in temperate (P = 0.018) and warm (P = 0.007) conditions. Resting heart rate was significantly elevated by NERI (18 degrees C: P = 0.02; 30 degrees C: P = 0.018). In Rebox18, heart rate was significantly higher than in the Pla18, while in the heat no effect of the drug treatment was reported during exercise. In Rebox30, all hormone concentrations increased during exercise, except for growth hormone (GH), which was significantly lower during exercise. In Rebox18, prolactin (PRL) concentrations were significantly elevated; GH was significantly higher at rest, but significantly lower during exercise. In conclusion, manipulation of the NE system decreases performance and modifies hormone concentrations, thereby indicating a central NE effect of the drug. These findings confirm results from previous studies that predominantly increased DA activity is important in improving performance.

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“…For example, we observed a reduction rather than an increase in the response to cold-pressor and handgrip testing (23,26,32). This paradoxical response is probably explained by a sympatholytic effect in the brain.…”

Section: Discussionmentioning

confidence: 62%

Phenotypical evidence for a gender difference in cardiac norepinephrine transporter function

Schroeder

Adams²,

Boschmann³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

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Norepinephrine transporter (NET) function has a central role in the regulation of synaptic norepinephrine concentrations. Clinical observations in orthostatic intolerance patients suggest a gender difference in NET function. We compared the cardiovascular response to selective NET inhibition with reboxetine between 12 healthy men and 12 age-matched women. Finger blood pressure, brachial blood pressure, and heart rate were measured. The subjects underwent cardiovascular autonomic reflex testing and a graded head-up tilt test. In a separate study, we applied incremental concentrations of tyramine and isoproterenol through subcutaneous microdialysis catheters in eight men and in eight women. NET inhibition elicited a threefold greater increase in supine blood pressure in men than women (P < 0.05). The pressor response was driven by an increased cardiac output. The orthostatic heart rate increase during NET inhibition was greater in men than women (56 +/- 5 beats/min in men, 42 +/- 4 beats/min in women, P < 0.001). In contrast, NET inhibition resulted in a similar suppression in the cold pressor and handgrip response, low-frequency blood pressure oscillations, and venous norepinephrine in the supine position. Men and women were similarly sensitive to the lipolytic effect of isoproterenol and tyramine. We conclude that NET inhibition results in more pronounced changes in cardiac regulation in men than women. Our observations suggest that the NET contribution to cardiac norepinephrine turnover may be decreased in women. The gender difference in NET function may not be expressed in tissues that are less NET dependent than the heart.

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The effects of reboxetine, a noradrenaline reuptake inhibitor, on the plasma noradrenaline response to a cold pressor test in healthy volunteers

Cited by 6 publications

References 26 publications

Atomoxetine Attenuates Dextroamphetamine Effects in Humans

Atomoxetine Attenuates Dextroamphetamine Effects in Humans

Acute norepinephrine reuptake inhibition decreases performance in normal and high ambient temperature

Phenotypical evidence for a gender difference in cardiac norepinephrine transporter function

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