Disease relevance of Reboxetine

• Reboxetine and hyponatremia [1].
• Attenuation of olanzapine-induced weight gain with reboxetine in patients with schizophrenia: a double-blind, placebo-controlled study [2].
• Patients given olanzapine and reboxetine demonstrated a significantly lower increase in body weight (mean=2.5 kg, SD=2.7) than those given olanzapine and placebo (mean=5.5 kg, SD=3.1) [2].
• Effect of reboxetine on depression in Parkinson's disease patients [3].
• Dry mouth, insomnia, blurred vision, sweating, and constipation were recorded more frequently in the reboxetine group than in the placebo group [4].

Psychiatry related information on Reboxetine

• There were no significant differences between groups in age, sex, duration or severity of disease or psychopathology, or reboxetine dose or plasma levels [5].
• CONCLUSIONS: Reboxetine and fluoxetine appear to have similar effects on depressive symptoms [6].
• CONCLUSION: Reboxetine was effective and well tolerated in the treatment of panic disorder [7].
• Comprehensive clinical trials, including 8 placebo-controlled and/or active treatment-controlled studies, plus 4 open studies, have assessed the short-term and long-term efficacy and tolerability of reboxetine in patients with major depressive disorders and dysthymia [8].
• STUDY OBJECTIVES: To investigate potential stimulant and anticataplectic effects of 10 mg reboxetine in patients diagnosed with narcolepsy [9].

High impact information on Reboxetine

• The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine [5].
• RESULTS: In the facial expression recognition task, citalopram and reboxetine reduced the identification of the negative facial expressions of anger and fear [10].
• CONCLUSIONS: The selective norepinephrine reuptake inhibitor reboxetine may reduce olanzapine-induced weight gain in schizophrenia patients, and activation of the adrenergic system may attenuate weight gain induced by atypical antipsychotic agents [2].
• Interestingly, in HI, the same drugs also decreased the editing levels of either the flip (desipramine) or flop (reboxetine) form of GluR3 [11].
• RESULTS: Our data showed that fluoxetine and desipramine exerted moderate but selective effects on glutamate receptor expression and editing, while reboxetine appeared to be the drug that affects glutamate receptors (GluR) most [11].

Chemical compound and disease context of Reboxetine

• Reboxetine (40 mg/kg/day), citalopram (10 mg/kg/day), voluntary physical activity, and the combination of antidepressants with exercise were applied to rats for a range of treatment intervals (2 to 14 days) [12].
• CONCLUSIONS: Study observations indicate comparable efficacy of reboxetine and fluvoxamine in the management of MVA-related PTSD despite reboxetine's selective noradrenergic activity [13].
• Influence of reboxetine on salivary MHPG concentration and cognitive symptoms among patients with alcohol-related Korsakoff's syndrome [14].
• 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 [15].
• Overall, paroxetine and escitalopram exhibited the least sleep disruptive profiles, whereas duloxetine, venlafaxine, and reboxetine increased the time spent awake and suppressed paradoxical sleep [16].

Biological context of Reboxetine

• The pharmacokinetics of reboxetine and its enantiomers were also investigated in the study [17].
• As expected, heart rate increased from baseline (approximately 8-11 beats/min) at > or =8 mg reboxetine daily [18].
• Increases in supine blood pressure after reboxetine administration may be interpreted as regression to the mean value and not caused by any treatment effect [17].
• There was no significant difference between the maximum plasma concentration, mean time to maximum plasma concentration, plasma half-life, or area under the plasma concentration-time curve (AUC) of the R,R-enantiomer after reboxetine or R,R-enantiomer administration [17].
• At rest, energy expenditure and substrate oxidation rates did not differ between reboxetine and placebo treatment [19].

Anatomical context of Reboxetine

• Reboxetine administration did not affect expression of GAD65/67 mRNA in handled rats; however, administration to stressed animals reduced GAD67 (but not GAD65) mRNA in the medial amygdaloid nucleus, posteromedial bed nucleus of the stria terminalis, and dentate gyrus [20].
• Doses of 10 mg/kg/day reboxetine through subcutaneous osmotic pumps for 2 days increased extracellular NA by 272% in the dorsal hippocampus (DH) of rats [21].
• We previously reported that reboxetine and desipramine, two selective norepinephrine transporter (NET) blockers, at doses that maximally increase DA in the prefrontal cortex, do not increase DA in the parietal and occipital cortices [22].
• On the contrary, reboxetine did not increase further the dopamine output produced by GBR 12909 in the nucleus accumbens core or in the dorsal caudate, areas lacking a consistent noradrenergic innervations [23].
• The distribution of reboxetine appears to be limited to a fraction of the total body water due to its extensive (>97%) binding to plasma proteins [24].

Associations of Reboxetine with other chemical compounds

• RESULTS: Reboxetine is a potent, selective, and specific norepinephrine reuptake inhibitor (selective NRI) as determined by both in vitro and in vivo measurements [25].
• METHODS: Eleven healthy volunteers received (1) 4 mg reboxetine orally on the second day of a 5-day regimen of 200 mg ketoconazole once daily and (2) 4 mg reboxetine orally in a crossover design [26].
• In controls and reboxetine-treated rats, 1 and 5 Hz stimulations of the afferent 5-HT bundle to the hippocampus, which allows determination of terminal 5-HT(1B) autoreceptor sensitivity, produced similar frequency-dependent decreases in pyramidal neuron firing in both groups [27].
• Quinidine does not affect the in vivo clearance of reboxetine, confirming the lack of involvement of CYP2D6 [24].
• Comparative evaluation of positron emission tomography radiotracers for imaging the norepinephrine transporter: (S,S) and (R,R) enantiomers of reboxetine analogs ([11C]methylreboxetine, 3-Cl-[11C]methylreboxetine and [18F]fluororeboxetine), (R)-[11C]nisoxetine, [11C]oxaprotiline and [11C]lortalamine [28].

Gene context of Reboxetine

• The lack of effect of reboxetine on CYP2D6 and CYP3A4 was confirmed by the lack of effect on the metabolism of dextromethorphan and alprazolam in healthy volunteers [24].
• Reboxetine at therapeutic concentrations has no effect on the in vitro activity of CYP1A2, 2C9, 2D6, 2E1 or 3A4 [24].
• Based on the results of the study, it is concluded that the metabolism of both reboxetine enantiomers in humans is principally mediated via CYP3A [29].
• The CYP2C19 genotype (only heterozygosity) had no influence on reboxetine and paroxetine pharmacokinetics [30].
• We investigated how different drugs (fluoxetine (FLX), desipramine (DMI), reboxetine (RBX)) affect CREB expression and phosphorylation of Ser(133) in the hippocampus and prefrontal/frontal cortex (PFCX) [31].

Analytical, diagnostic and therapeutic context of Reboxetine

• Rats were exposed to repeated unavoidable stress for 21 days, with or without reboxetine treatment, and then were tested for escape; 2 days later they were implanted with microdialysis probes in the NAcS [32].
• Data were obtained from four prospective, double-blind, randomized, placebo-controlled clinical trials of the efficacy of reboxetine (8 to 10 mg/d) over 4 to 8 weeks in patients with major depression [33].
• Since pure enantiomers of reboxetine were not available, they were obtained from the racemic powder by means of direct-phase, high-performance liquid chromatography and their identity confirmed by circular dichroism spectra [34].
• Residual symptoms in depressed patients after treatment with fluoxetine or reboxetine [35].
• Reboxetine is well absorbed after oral administration [24].

References