The human pharmacology of reboxetine

Abstract

Reboxetine is a novel antidepressant with a potent noradrenaline uptake-inhibiting property, but with little anity for neurotransmitter receptors. Desipramine is a classical tricyclic antidepressant which, apart from inhibiting noradrenaline uptake, also has anity for muscarinic cholinoceptors and a 1 -adrenoceptors, which can result in unwanted side eects. Single doses of reboxetine (1, 2 and 4 mg) and desipramine (25, 50 and 100 mg), were compared with placebo in 37 healthy volunteers, on several autonomic functions. Reboxetine antagonised tyramineevoked mydriasis, indicating noradrenaline-uptake blockade in the iris. The antidepressant increased blood pressure, heart rate, and resting pupil diameter and shortened the recovery time of the light re¯ex response consistent with a sympathomimetic eect resulting from noradrenaline-uptake blockade in peripheral tissues. Both antidepressants reduced salivation and light re¯ex amplitude, but failed to antagonise pilocarpine-evoked miosis, a response mediated by muscarinic cholinoceptors. Therefore, the eects on salivation and light re¯ex amplitude are unlikely to be due to muscarinic receptor blockade, but may rather re¯ect enhancement of noradrenergic inhibition of central parasympathetic nuclei as a result of noradrenaline-uptake blockade. Both antidepressants failed to antagonise phenylephrine-evoked sweating and methoxamine-evoked mydriasis, responses mediated by a 1 -adrenoceptors,

The effects of reboxetine and venlafaxine on ECG variables in depressed patients / Depresyon hastalarında reboksetin ve venlafaksinin EKG değişkenleri üzerine etkisi

“…The significant increase in heart rate with reboxetine treatment in this study is in line with previous studies (27,28). The accelerated heart rate had been previously attributed to the sympathomimetic activity of reboxetine (29). On the other hand, there was a trend of association between venlafaxine and increased heart rate although this was not clinically or statistically significant.…”

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

“…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). The accelerated heart rate has been attributed to sympathomimetic activity due to NE reuptake inhibition (34), but it has also been hypothesized that NE reuptake inhibition augments central NE inhibition in parasympathetic nuclei, thereby lowering the cardiac parasympathetic tone and increasing heart rate (32). Inhibition of NE reuptake increased heart rate compared with the Pla trial during the fixed-intensity exercise in normal environmental temperature; this difference disappeared from the moment that the subjects were free to change their power output, which was significantly lower during the trials with NE reuptake inhibition and was accompanied by lower blood lactate concentrations.…”

“…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).…”

Effects of Reboxetine on Sleep and Nocturnal Cardiac Autonomic Activity in Patients with Dysthymia

“…After 1-day and 7-day treatment, reboxetine showed mild, not significant, increases of LF component and LF/HF ratio, as well as a mild, not significant, decrease of HF component. These effects are consistent with recent investigations that indicated an increase in heart rate and blood pressure after acute treatment with reboxetine in healthy volunteers (Szabadi et al, 1998;Denolle et al, 1999). Some authors have attributed the accelerated heart rate to a sympathomimetic activity of reboxetine (Szabadi et al, 1998).…”