Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several treatment approaches are available for treatment of depression. However, reboxetine is the first selective noradrenaline re-uptake inhibitor. Whereas formerly only noradrenaline re-uptake inhibitors with a mixed mechanism of action were available. These included action not only at noradrenergic, but also at serotonergic and other neurotransmitter-sites. Thus, reboxetine represents the first of a new class of antidepressant agents with specificity for the noradrenergic system. Reboxetine has been shown to be an effective first-line treatment for patients with all grades of depression, to be effective in the prevention of relapse and recurrence and to offer significant benefits in terms of relieving the impaired social functioning associated with depressive disorders. Reboxetine was significantly superior to the serotonergic compound fluoxetine in improvement of social functioning in both the general depressed population and in those patients who achieved symptomatic remission, indicating a superior quality of remission. Altogether reboxetine was well tolerated during the acute and long-term treatment phase; side-effects such as increased sweating, constipation and dry mouth were the most prominent to be reported. The availability of reboxetine represents a significant addition to the currently available pharmacologic armamentarium for the treatment of depression.
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PMID:Reboxetine: the first selective noradrenaline re-uptake inhibitor. 1124 15

Central dopaminergic neurons have been suggested to be involved in the pathophysiology of several psychiatric disorders, including depression, and appear to be modulated by noradrenergic activity both at the nerve terminal level and at the somatodendritic level. In recent years reboxetine, a selective noradrenaline reuptake inhibitor that differs from tricyclic antidepressants by its low affinity for muscarinic, cholinergic and alpha(1)-adrenergic receptors, has been introduced clinically. In the present study the effect of reboxetine on the function of the mesolimbocortical dopamine system was investigated by means of single cell recording and microdialysis in rats following administration of reboxetine in doses that appear to yield clinically relevant plasma concentrations. Reboxetine (0.625--20 mg/kg intravenously) induced an increase in burst firing, but not in average firing frequency of dopamine (DA) cells in the ventral tegmental area (VTA). Moreover, reboxetine (0.15--13.5 mg/kg intraperitoneally) caused a significantly enhanced DA output in the medial prefrontal cortex, whereas no effect was observed in the nucleus accumbens. Local administration of reboxetine (333 microM, 60 min), by means of reversed microdialysis into these brain regions, caused a significant increase in DA output in both brain regions. However, local administration of reboxetine into the VTA (333 microM, 60 min) did not affect DA availability in these terminal areas. Our results imply that clinical treatment with reboxetine may result in facilitation of both prefrontal DA output and the excitability of VTA DA neurons, effects that may contribute to its antidepressant action, especially on drive and motivation.
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PMID:Reboxetine modulates the firing pattern of dopamine cells in the ventral tegmental area and selectively increases dopamine availability in the prefrontal cortex. 1130 41

This paper investigates if the highly selective norepinephrine reuptake inhibitor reboxetine leads to a dose-dependent cortisol release and if this response depends on personality dimensions related to clinical depression in healthy volunteers. Twenty-four male subjects received placebo, 2 mg, or 4 mg reboxetine in a balanced, randomized cross-over study. Cortisol was measured in saliva at six different time-points according to the kinetics of the drug. Furthermore, several measurements of cardiovascular parameters, emotional states, and possible side-effects were obtained. Subjects were divided into two groups scoring above or below the median of a depressiveness questionnaire scale [n = 11, low (D-); n = 13, high (D+)]. Results clearly demonstrated, that reboxetine stimulates cortisol release. Whereas blood pressure was not affected, heart rate increased after 2 and 4 mg but not dose dependently. Subjects reported more non-specific arousal while the dimensions of tiredness-wakefulness and positive-negative emotional states were not affected by the drug. Somatic complaints were low and only non-specific complaints were statistically elevated but of negligible amount. Subjects classified as D+ can be characterized as high responders to the drug. This is especially true not only for cortisol increases but also for changes in heart rate and some ratings on physical complaints. Hot flushes, sweating and a throbbing sensation in blood vessels in the head were observed in D+ but only with the 4 mg dose. The results clearly demonstrate that reboxetine stimulates cortisol release and heart rate and that this is particularly pronounced in subjects scoring high on depression-related personality dimensions. Reboxetine, therefore, is a promising tool for investigating neuroendocrine response to noradrenergic challenge tests. The question whether increased responses in D+ are due to an up-regulation of receptor sensitivity as a consequence of low norepinephrine supply is discussed.
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PMID:Reboxetine in a neuroendocrine challenge paradigm: evidence for high cortisol responses in healthy volunteers scoring high on subclinical depression. 1134 96

The pharmacokinetic characteristics of reboxetine, a unique selective noradrenaline reuptake inhibitor (selective NRI) for the treatment of depression, were studied in 12 healthy, elderly volunteers (mean age 81 years +/- 9 years). All subjects received a single 4-mg dose of reboxetine, and plasma reboxetine concentrations were measured by HPLC. Reboxetine was well tolerated by all subjects. Exposure to reboxetine was higher in this group of very elderly subjects, compared with data obtained in a similar study of young, healthy volunteers. Cmax in the elderly was 271 +/- 86 ng/ml, compared with 111 +/- 28 ng/ml in the young subjects after a single 4-mg dose, although in both groups Cmax was observed after 2 h. The AUC infinity was nearly four times that in the younger subjects (8345 +/- 3107 ng.h/ml vs. 2106 +/- 881 ng.h/ml) and the t1/2 was twice as long (24 +/- 6 h vs. 12 +/- 3 h). Renal clearance was also reduced. Reboxetine 8-10 mg/day has been effective and well tolerated in clinical trials in non-elderly depressed patients. The increased exposure to reboxetine observed in our very elderly subjects supports a reduction of the starting dose to 4 mg/day (in two divided doses) in the elderly.
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PMID:Pharmacokinetics of reboxetine in healthy, elderly volunteers. 1142 Aug 89

Reboxetine is the first selective norepinephrine reuptake inhibitor (NRI) approved for the treatment of major depressive disorder (MDD). Although reboxetine has demonstrated efficacy for the treatment of depression, its effects on specific depressive symptoms have not been reported. We evaluated the effects of reboxetine on four Hamilton Depression Rating Scale (HAM-D) factors: psychomotor retardation, anxiety, cognitive disturbance and insomnia. Data were obtained from four short-term (4-8-week), randomized, placebo-controlled trials of reboxetine for the treatment of MDD. For each study, mean changes in HAM-D symptom factor scores from randomization to the study endpoint were compared between reboxetine and placebo. In addition, data from all four studies were pooled to determine the proportions of patients who either improved or worsened with treatment were compared between placebo (n = 353) and reboxetine (n = 350) treatment groups. Compared to placebo, reboxetine significantly improved psychomotor retardation in all four trials. Cognitive disturbance and anxiety were improved in three of four trials, and insomnia was improved in one trial with a positive trend in the second trial. Reboxetine, a selective NRI, improves symptoms of psychomotor retardation, anxiety and cognitive disturbance during treatment of MDD.
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PMID:Effects of reboxetine on Hamilton Depression Rating Scale factors from randomized, placebo-controlled trials in major depression. 1189 Jan 85

Reboxetine is a new norepinephrine reuptake inhibitor (NRI) drug recently introduced in the therapy for depressed patients. It is effective in the treatment of severe depression and safer to use than traditional tricyclic antidepressants. In this paper an original high-performance liquid chromatography (HPLC) method with ultraviolet detection for the determination of reboxetine in human plasma is described. It uses a C8 reversed-phase column and a mobile phase composed of acetonitrile and aqueous tetramethylammonium perchlorate. For the analysis of plasma samples containing very low levels of reboxetine, another HPLC method with fluorimetric detection was developed (limit of quantitation, LOQ=11 ng ml(-1); limit of detection, LOD=4 ng ml(-1)). The fluorimetric method is based on precolumn derivatisation of reboxetine with 9-fluorenylmethyl chloroformate. An accurate sample pretreatment of human plasma samples has been implemented by means of solid-phase extraction (SPE) on Oasis HLB (hydrophilic-lipophilic balance) cartridges with very high extraction yields (>95%). Both methods were applied to the analysis of plasma samples from depressed patients undergoing therapy with reboxetine and gave satisfactory results in terms of precision (RSD<4.5%) and accuracy (mean recovery>94%).
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PMID:Determination of reboxetine, a recent antidepressant drug, in human plasma by means of two high-performance liquid chromatography methods. 1199 39

The clinical profile of reboxetine, a selective noradrenaline reuptake inhibitor, was compared with that of the selective serotonin reuptake inhibitor fluoxetine and placebo in a double-blind, multicenter, parallel-group clinical trial of patients with major depression. Among the 381 patients treated with reboxetine 8 to 10 mg/day, fluoxetine 20 to 40 mg/day, or placebo for up to 8 weeks, a statistically significant greater reduction in the mean Hamilton Rating Scale for Depression (21-item HAM-D) total score (the primary efficacy variable) was seen for both active treatment groups compared with placebo (p < 0.024). A significantly greater proportion of patients treated with either reboxetine or fluoxetine also achieved a response (>or=50% reduction in HAM-D) or remission (HAM-D <or=10 points) than those who received placebo (p < 0.01 for both analyses). Similar findings were recorded in a subpopulation of severely ill patients, with statistically significantly greater decreases in the mean HAM-D total score between both active treatment groups compared with placebo (p < 0.024). Additional efficacy assessments (Montgomery-Asberg Depression Rating Scale, Clinical Global Impression) reflected the primary efficacy analysis, with both active treatments offering comparable efficacy that was superior to that of placebo. Reboxetine and fluoxetine are more effective than placebo in the treatment of major depression. Futhermore, both antidepressants are well tolerated but possess different adverse event profiles.
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PMID:Reboxetine, a new noradrenaline selective antidepressant, is at least as effective as fluoxetine in the treatment of depression. 1217 39

Reboxetine is a novel antidepressant with a selective action on noradrenaline. In addition to its efficacy in depression, it has been found to improve social adaptation. The objective of this study was to assess the specific social behavioural effects of reboxetine which might be associated with social adaptation. Ten pairs of healthy volunteers took part in a randomized double-blind, crossover study of 2 weeks treatment with reboxetine (4 mg b.d.) and placebo with a 2-week washout period. In each pair, one person (subject) took the tablets and the other (flatmate) received no treatment. On the last day of each treatment period, the subjects socially interacted with a stranger (a confederate behaving as a responsive person) in a stranger-dyadic social interaction paradigm. After the interaction, subjects played the Mixed-Motive game, which measures cooperative behaviour and communication, with the confederate. Subjects read a short story before and after the social interaction. The flatmates evaluated the social behaviour of the subjects before and at the end of the two treatment periods. On reboxetine, the subjects were rated to be significantly more agreeable and cooperative (passive participant) and less submissive by their flatmates. They showed significantly less eye contact with the confederate in the social interaction paradigm and gave significantly fewer helplessness messages during the game. They spoke faster on the reading task after the social interaction. This study provides evidence that reboxetine increases cooperative social behaviour and increases social drive, which might be important for social adaptation.
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PMID:Reboxetine promotes social bonding in healthy volunteers. 1287 May 66

Reboxetine is a selective noradrenaline reuptake inhibitor that has been found to be efficacious and tolerable in both short- and long-term treatment of depression. It is a racemic mixture of two enantiomers, the (S,S)-enantiomer being the more potent inhibitor. Reboxetine has little effect on 5-HT or dopamine reuptake, does not inhibit monoamine oxidase activity and has low affinity for alpha-adrenergic and muscarinic receptors. Absorption is rapid and the terminal elimination half-life (13 h) allows twice-daily administration. It shows linear pharmacokinetics which are unaffected by multiple dosing, gender or hepatic insufficiency, although doses should be reduced in elderly patients and in those with severe renal impairment. Reboxetine does not interact with the principal isotypes of the cytochrome P450 system and should have a low potential for drug-drug interactions. Studies in animal models indicate that it has low toxicity.
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PMID:Reboxetine, a selective noradrenaline reuptake inhibitor for the treatment of depression. 1297 68

Reboxetine is a specific norepinephrine transporter (NET) inhibitor and has been marketed in several countries as a racemic mixture of the (R,R) and (S,S) enantiomers for the treatment of depression. Its methyl analog (methylreboxetine, MRB) has been shown to be more potent than reboxetine itself. We developed a nine-step synthetic procedure to prepare the normethyl precursor, which was used to synthesize [11C]O-methylreboxetine ([11C]MRB). We also developed a convenient resolution method using a chiral HPLC column to resolve the racemic precursor to obtain enantiomerically pure individual precursors that lead to the individual enantiomers (R,R)-[11C]MRB and (S,S)-[11C]MRB. Here we report an evaluation of the racemate and individual enantiomers of [11C]MRB as radioligands for PET imaging studies of NET systems in baboons both in brain and in peripheral organs. The relative regional distribution of the radioactivity after injection of [11C]MRB in baboon brain is consistent with the known distribution of NET. For a NET-poor region such as striatum, there were no significant changes in the striatal uptakes with and without the nisoxetine pretreatment. In contrast, a significant blocking effect was observed in NET-rich regions such as thalamus and cerebellum after injection of racemic [11C]MRB, with an even more dramatic effect after injection of (S,S)-[11C]MRB. These results, along with the fact that there was no regional specificity and no blocking effect by nisoxetine for (R,R)-[11C]MRB, suggest the enantioselectivity of MRB in vivo, consistent with previous in vitro and in vivo studies in rodents. PET studies of baboon torso revealed a blocking effect by desipramine only in the heart, a NET-rich organ, after injection of (S,S)-[11C]MRB, but not the (R,R)-isomer. These studies demonstrate that the use of (S,S)-[11C]MRB would allow a better understanding of the role that NET plays in living systems.
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PMID:Evaluation of a new norepinephrine transporter PET ligand in baboons, both in brain and peripheral organs. 1455 39


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