Effects Of Reboxetine Research Articles

P.1.057 Contrasting effects of reboxetine and fluoxetine on regional expression of Fos-like immunoreactivity in the rat forebrain

P.1.057 Contrasting effects of reboxetine and fluoxetine on regional expression of Fos-like immunoreactivity in the rat forebrain

Reboxetine modulates norepinephrine efflux in the frontal cortex of the freely moving rat: the involvement of α 2 and 5-HT 1A receptors

The effect of reboxetine on norepinephrine (NE) efflux in the frontal cortex of freely moving rats has been studied using in vivo microdialysis. Reboxetine was administered either by injection (10 and 30 mg/kg i.p.) or directly to the frontal cortex via the dialysis probe (10 and 100 μM). To further elucidate the mechanism of action of reboxetine in this region yohimbine (10 μM) was co-infused with reboxetine via the frontal cortex probe. Both routes of administration of reboxetine resulted in a drug-induced, dose-dependent decrease in frontal cortex NE efflux. This effect was reversed following co-infusion of yohimbine, which has been shown to possess both α 2-adrenoceptor antagonist and 5-HT 1A agonist properties.

Effects of reboxetine on sympathetic neuroeffector transmission in rabbit carotid artery.

The effect of reboxetine on sympathetic neuroeffector transmission in rabbit isolated carotid artery was examined. Reboxetine (10-8-3 x 10-6 M) and cocaine (10-6-3 x 10-5 M), but not desipramine (10-8-3 x 10-7 M), increased contractions evoked by electrical field stimulation. At higher concentrations, reboxetine (10-4 M), cocaine (3 x 10-4 M), and desipramine (3 x 10-7-10-5 M) inhibited the neurogenic contractions. The enhancement seen with reboxetine and cocaine was partially reversible, whereas the inhibition was readily reversible. Reboxetine (10-7 M) and cocaine (10-5 M) prevented the inhibitory action of bretylium (10-6 M). Reboxetine (10-8-10-5 M), desipramine (10-7-10-4 M), and cocaine (10-6-10-5 M) increased the stimulation-evoked [3H]norepinephrine release. Pargyline (5 x 10-4 M) augmented the facilitatory effect of reboxetine (3 x 10-9-10-6 M) and cocaine (10-7-3 x 10-5 M). Reboxetine (10-8-10-6 M), desipramine (10-8-10-6 M), and cocaine (3 x 10-8-10-5 M) reduced the [3H]norepinephrine (10-8 M) uptake. Reboxetine (10-7 M) and cocaine (10-5-2 x 10-4 M) enhanced the contractions evoked by phenylephrine and norepinephrine. Higher concentrations of reboxetine antagonized the contractions. Reboxetine (10-5-6 x 10-5 M) antagonized the contractions evoked by potassium. The contractions evoked by tyramine (3 x 10-6-10-3 M) was reduced by reboxetine (3 x 10-8-10-6 M) and by cocaine (10-7-10-5 M). We conclude that reboxetine inhibits the membrane amine pump (uptake-1) in the terminals of postganglionic adrenergic neurons in a cocaine-like manner.

The effects of reboxetine on human sleep architecture in depression: preliminary results

The effects of reboxetine on human sleep architecture in depression: preliminary results

Effects of reboxetine, a selective norepinephrine reuptake inhibitor, on sympathetic and parasympathetic outflow to the heart: preliminary data.

Antidepressants exert distinct effects on cardiac autonomic nervous system (ANS) function, depending on their receptor profile. Reboxetine is a selective norepinephrine (NE) reuptake inhibitor and shows only low affinity for adrenergic and muscarinic receptors. Data on reboxetine's effects on ANS function in patients with major depression (MD) are sparse. This study evaluates the effects of reboxetine on cardiac ANS function assessed by standardized measurements of heart rate variability (HRV). Twenty-five MD patients (DSM-III-R) underwent serial ANS function tests ( n = 94) including conventional electrocardiograms and standardized measurements of HRV and blood pressure prior to reboxetine treatment as well as on days 2, 10 and 21 during reboxetine therapy. The starting dose was 4 mg; on day 10, reboxetine was increased to 8 mg/day. The effects of reboxetine on ANS function were evaluated using the paired Wilcoxon test. Reboxetine treatment was associated with 1) a significant decrease in absolute and relative low-frequency power as well as in mean arterial pressure on day 2, and 2) a significant decrease in the average low- to high-frequency ratio on days 2 and 10. No significant changes in any of the vagally mediated HRV indices occurred. These preliminary findings are compatible with the hypothesis that inhibition of brain NE reuptake by reboxetine resulted in an inhibition of central noradrenergic activity via a local increase of NE concentration at inhibitory alpha(2)-autoreceptors. Long-term treatment (21 days) may cause desensitization and down-regulation of alpha(2)-autoreceptors, so that attenuation of the inhibitory restraint on sympathetic outflow results.

Noradrenergic lesions differentially alter the antidepressant-like effects of reboxetine in a modified forced swim test

The novel antidepressant reboxetine is a selective norepinephrine reuptake inhibitor. In this study, the antidepressant-like effects of reboxetine were characterized in a modified rat forced swim test. Further, in order to investigate the role of the locus coeruleus and lateral tegmental noradrenergic systems in the mediation of reboxetine's effects, the impact of different chemical lesions of these two pathways was examined on the behavioral responses induced by reboxetine in the forced swim test. Reboxetine (5–20 mg/kg, s.c.) dose-dependently decreased immobility and swimming behavior in the forced swim test while it simultaneously increased climbing behavior. These effects were similar to those previously demonstrated with tricyclic antidepressants and are indicative of reboxetine's effects on the noradrenergic system. Discrete local injections of the neurotoxin 6-hydroxydopamine were employed to lesion the ventral noradrenergic bundle arising from cells located in the lateral tegmentum. This resulting lesion completely prevented reboxetine (10 mg/kg, s.c.)-induced decreases in immobility and increases in climbing behavior, demonstrating that an intact ventral noradrenergic bundle is required for the manifestation of reboxetine-induced antidepressant-like behavior in the test. In contrast, lesions of the dorsal noradrenergic bundle which consists of neurons arising from the nucleus locus coereleus, were achieved by systemic pretreatment with the selective noradrenergic neurotoxin N-(2-chloroethyl)- N-2-bromobenzylamine (DSP-4; 50 mg/kg, i.p.). The ability of reboxetine (10 mg/kg, s.c.) to increase climbing and decrease immobility was augmented by DSP-4 pretreatment. Furthermore, neither lesions of the dorsal noradrenergic bundle nor the ventral noradrenergic bundle altered baseline immobility scores in the forced swim test. Taken together, these data suggest that forebrain regions innervated by these two distinct noradrenergic pathways exert opposing influences on the behavioral response to reboxetine in the rat forced swim test.

No effect of reboxetine on plasma concentrations of clozapine, risperidone, and their active metabolites.

The effect of reboxetine on steady-state plasma concentrations of the atypical antipsychotics clozapine and risperidone was studied in 14 patients with schizophrenia or schizoaffective disorder with associated depressive symptoms. Seven patients stabilized on clozapine therapy (250-500 mg/day) and seven receiving risperidone (4-6 mg/day) were given additional reboxetine (8 mg/day). After 4 weeks of reboxetine therapy, mean plasma concentrations of clozapine, norclozapine, and risperidone active moiety (sum of concentrations of risperidone and 9-hydroxyrisperidone) increased slightly but not significantly by 5%, 2%, and 10%, respectively. The mean plasma clozapine/norclozapine and risperidone/9-hydroxyrisperidone ratios were not modified during reboxetine treatment. Reboxetine coadministration with either clozapine or risperidone was well tolerated. These findings indicate that reboxetine has minimal effects on the metabolism of clozapine and risperidone and may be added safely to patients receiving maintenance treatment with these two antipsychotics.

No effect of reboxetine on plasma concentrations of clozapine, risperidone and their active metabolites in patients with schizophrenia

No effect of reboxetine on plasma concentrations of clozapine, risperidone and their active metabolites in patients with schizophrenia

Chronic treatment with reboxetine by osmotic pumps facilitates its effect on extracellular noradrenaline and may desensitize alpha(2)-adrenoceptors in the prefrontal cortex.

1. This study investigated the effect of acute (2 days) and chronic (14 days) treatment with a selective inhibitor of noradrenaline uptake, reboxetine (10 mg kg(-1) day(-1)) by osmotic pumps, on extracellular noradrenaline and the sensitivity of alpha(2)-adrenoceptors in the prefrontal cortex of rats. 2. The effect of continuous infusion of reboxetine for 14 days on cortical extracellular noradrenaline was significantly higher (599% of vehicle levels) than after 2 days (263% of vehicle levels). 3. Brain concentrations of reboxetine after 2 and 14 days of infusion were 37.9+/-17.8 and 37.1+/-7.7 ng g(-1), respectively. 4. Reboxetine infused for 2 and 14 days significantly increased extracellular dopamine in the prefrontal cortex, to a similar extent (257 and 342% of vehicle levels, respectively), whereas extracellular 5-HT was not modified by either treatment. 5. Clonidine (10 and 30 microg kg(-1) i.p.) reduced cortical extracellular noradrenaline similarly in animals treated with reboxetine or vehicle for 2 days whereas the effects in rats infused with reboxetine for 14 days were markedly less than in vehicle-treated animals. 6. Clonidine (0.05 and 0.2 microM), infused through the dialysis probe into the prefrontal cortex, reduced cortical extracellular noradrenaline much less in rats treated with reboxetine for 14 days than in vehicle-treated animals. 7. Reboxetine's effect on extracellular noradrenaline in the prefrontal cortex was greater after chronic treatment and could be associated with desensitization of terminal alpha(2)-adrenoceptors that normally serve to inhibit noradrenaline release.

Reboxetine effects on cognitive functioning in depressed patients

Reboxetine effects on cognitive functioning in depressed patients

Effects of reboxetine and sertraline treatments alone and in combination on the binding properties of cortical NMDA and beta1-adrenergic receptors in an animal model of depression.

Changes to the binding properties of cortical N-methyl-D-aspartic acid (NMDA) and beta-adrenergic receptors have both been reported as potential indicators of antidepressant activity. In the present investigation we examined the effects of the noradrenaline reuptake inhibitor, reboxetine, the serotonin reuptake inhibitor, sertraline, alone and in combination on the binding properties of cortical NMDA receptors and cortical beta1-adrenoceptors following 14 days of treatment in the olfactory bulbectomized rat model of depression. A decrease in the potency of glycine to displace the strychnine insensitive glycine antagonist [3H] 5,7 dichlorokynurenic acid (5,7 DCKA) was observed in cortical homogenates of OB rats when compared to sham-operated controls. Similarly, treatment with the combination of reboxetine and sertraline for 14 days produced a decrease in the potency of glycine when compared to vehicle treated controls. By contrast neither olfactory bulbectomy or drug treatment significantly altered basal or glycine enhanced binding of the non-competitive NMDA antagonist [3H] MK-801 in cortical homogenates. Reboxetine alone, and in combination with sertraline, down-regulated [3H]-CGP 12177 (a selective beta-adrenoceptor antagonist) binding in both OB and sham-operated animals. The lack of a bulbectomy effect in the [3H] CGP-12177 binding assay, and the fact that olfactory bulbectomy and antidepressant treatments produce a similar change to the potency of glycine at the NMDA receptor, suggests that these tests do not provide a neurochemical marker for either the behavioral hyperactivity deficit or antidepressant response in the model.

Effects of reboxetine and sertraline treatments alone and in combination on the binding properties of cortical NMDA and β 1-adrenergic receptors in an animal model of depression

Effects of reboxetine and sertraline treatments alone and in combination on the binding properties of cortical NMDA and β 1-adrenergic receptors in an animal model of depression

Effects of reboxetine and paroxetine compared to placebo on cognitive processes in healthy volunteers

Effects of reboxetine and paroxetine compared to placebo on cognitive processes in healthy volunteers

Effects of reboxetine on HAM-D factors among depressed patients

Effects of reboxetine on HAM-D factors among depressed patients

299. Urogenital and sexual effects of reboxetine: four single cases

299. Urogenital and sexual effects of reboxetine: four single cases

The selective noradrenaline re-uptake inhibitor reboxetine has an early onset of antidepressant action

INTRODUCTION: Most antidepressants take several weeks to demonstrate a therapeutic effect. We examined the time to onset of action of reboxetine, a unique selective noradrenaline re-uptake inhibitor (selective NRI). METHODS: In a multinational, multicentre, double-blind, parallel-group study, 56 inpatients with major depression were randomized to receive placebo or reboxetine titrated to 10 mg/day for 6 weeks. Efficacy was principally assessed by the Hamilton Depression Rating Scale. RESULTS: Reboxetine was associated with a significantly greater reduction in mean HAM-D total score from baseline to last assessment when compared with placebo. The effect of reboxetine separated from placebo at day 10 (P=0.006), indicated an early onset. In accordance with this observation, individual HAM-D item scores early showed significant improvements among patients treated with reboxetine when compared with those who received placebo: mood improved by day 10 (P=0.004), insomnia and interest in work and daily activities by day 14 (P=0.006 and 0.003, respectively) and somatic symptoms and anxiety by day 21 (P<0.001 in both cases). CONCLUSION: Reboxetine is an effective antidepressant with an early onset of action. Depressed mood is relieved first, followed by an improvement in interest in daily activities.

The influence of reboxetine on GH and PRL secretion in healthy subjects

Antidepressant drugs with different mechanism of action are known to have distinct influences on pituitary hormone secretion. Antidepressants which primarily act via noradrenaline (NA) reuptake inhibition (e.g. desipramine) stimulate growth hormone (GH) secretion, whereas serotonin (5 HT) reuptake inhibiting antidepressants (e.g. clomipramine, indalpine) are characterized by prolactin (PRL) stimulation. Cortisol (COR) secretion can be increased both by noradrenergic and serotonergic agonists. In this investigation the effects of acute po-administration of 4 mg reboxetine on the growth hormone (GH) and prolactin (PRL) secretion were examined in twelve physically and mentally healthy subjects, compared to placebo. Reboxetine is a new antidepressant which displays a selective noradrenaline reuptake inhibition. After insertion of an intravenous catheter, blood samples were drawn one hour prior to the administration of reboxetine or placebo, at time of application, and during the time of five hours after application in periods of 30 minutes. Plasma concentrations of GH, and PRL were determined in each blood sample. The AUC (AUC = area under the curve) value was used as parameter for the GH, and PRL response. In comparison to placebo, reboxetine caused a significant stimulation of GH secretion (p < 0.05). The GH stimulatory effects of reboxetine are probably mediated via noradrenergic a2-receptors. Unexpectedly, reboxetine significantly enhanced PRL secretion as well (p < 0.05). Since PRL secretion is known to be stimulated via serotonergic mechanisms and reboxetine is proven to be highly selective for noradrenaline reuptake inhibition, further studies have to be performed to clarify this result. Furthermore, a significant increase of the mean arterial blood pressure and the pulse rata could be demonstrated after application of 4 mg reboxetine 0, < 0.05).

The clinical pharmacologic profile of reboxetine: does it involve the putative neurobiological substrates of wellbeing?

Following a review of the clinical trials of reboxetine, a new nonadrenegic reuptake inhibitor antidepressant, this paper presents a heuristic theoretical framework to better understand selective antidepressant action. For over three decades, the dominant views of antidepressant action have seen these agents active across all constitutional types and regardless of social setting. An increasing number of studies using quality of life methods are at odds with this view. This paper summarizes several of these studies, along with two studies of the effects of reboxetine on the quality of life, which reveal differential effects of selective agents that demand alternative explanations to the conventional monoamine theories. The authors submit that any revisions in our understanding of what is happening will have to pay attention to temperamental inputs that antedate affective episodes and to the sense of wellbeing and level of residual symptoms patients have on treatment after the acute phase of their illness has remitted. Obviously much more research needs to be done in this area. This invited paper sketches out, in very general terms, some provocative possibilities of how future understanding of antidepressants, temperament and their neurobiologic substrates could lead to better matching of specific antidepressants to specific temperament types.

Effect of antidepressants on cognitive and psychomotor function: the lack of effect of reboxetine

Treatments available for depression vary in their side-effects. Behavioural toxicity, the alteration of psychomotor performance and cognitive function, can be counter-therapeutic, especially in elderly patients or those already cognitively compromised by their illness. This double-blind, 10-way crossover study in 10 healthy male volunteers compared the behavioural effects of reboxetine, a selective noradrenaline reuptake inhibitor, with amitriptyline and placebo, in the presence or absence of alcohol. Subjects were randomised to receive single doses of reboxetine (0·5 mg, 1 mg or 4 mg), amitriptyline (25 mg) or placebo, each subject acting as their own control with a 7 day washout period between treatments. Psychometric tests (including Critical Flicker Fusion threshold, Choice Reaction Time, and tests of tracking ability and short-term memory) were performed at baseline and for up to 9 hours post dose. Reboxetine had negligible effect on psychomotor or cognitive function compared with placebo and did not interact with alcohol. In contrast, amitriptyline alone and in combination with alcohol impaired CNS function even at this low dose. In conclusion, reboxetine has no disruptive effects on psychomotor performance or cognitive function even when combined with alcohol and thus has an important role to play in the treatment of depression. © 1998 John Wiley & Sons, Ltd.

Effect of antidepressants on cognitive and psychomotor function: the lack of effect of reboxetine

Effect of antidepressants on cognitive and psychomotor function: the lack of effect of reboxetine