norepinephrine reuptake ( Ki = 8.2 nM )

In vitro activity: Reboxetine completely and dose-dependently blocks [3H]-dopamine uptake to the human norepinephrine transporters (hNET) in Madin-Darby canine kidney (MDCK) cells, with a Ki value of 11 nM. [1]

Reboxetine potently and dose-dependently inhibits the firing of locus coeruleus neurons in rats with ED50 of 191 μg/kg. Piperoxan (1.5 mg/kg, IV), an α2 antagonist, can reverse the effects of reboxetine-induced inhibition of locus coeruleus neurons. The mice's blepharospasm and hypothermia caused by reserpine are reversed by reboxetine in a dose-dependent manner. Additionally, it is discovered that reboxetine counteracts the dose-dependent hypothermia in mice induced by clonidine. In rats, reboxetine (ED50 = 10 mg/kg and 3 mg/kg (p.o.)) reverses blepharospasm and hypothermia caused by reserpine.[1] In patients with DSM-III-R panic disorder, reboxetine significantly lowers the mean number of panic attacks and phobic symptoms. Additionally, reboxetine improves scores on the Sheehan Disability Scale, Hopkins Symptom Checklist-90, and Hamilton Rating Scale for Depression.[2] In patients with recurrent DSM-III-R major depression, reboxetine is linked to a significantly lower relapse rate than placebo (22% vs. 56%) and a higher cumulative probability of a maintained response during long-term treatment. After an episode ends, reboxetine effectively prevents depression symptoms from returning.[3] Reboxetine (0.3 mg/kg–20 mg/kg) administered systemically to rats dose-dependently raises extracellular norepinephrine in the frontal cortex, but has no effect on extracellular serotonin. The rat frontal cortex's extracellular dopamine is also increased by reboxetine (20 mg/kg). When Reboxetine is administered chronically for 14 days, the rat frontal cortex exhibits increased basal concentrations of extracellular norepinephrine and dopamine as well as a greater net increase in these substances—but not serotonin.[4] Reboxetine dose-dependently reduces the self-administration of nicotine by approximately 60%. Reboxetine (5.6 mg/kg) is administered repeatedly over the course of 14 sessions, which reduces nicotine self-administration and sucrose-maintained responding.[5]

Cell Line: SH-SY5Y cells
Concentration: 0.1 μM, 1 μM, 5 μM
Incubation Time: 24 hours
Result: Prevented the Dexamethasone-induced decreases in cell viability and proliferation rate.

Harlan-bred, male CF-1 mice (18-20 g), depression models
3 mg/kg, 30 mg/kg
Intraperitoneal injection

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Reboxetine is not approved for marketing in the United States by the U.S. Food and Drug Administration, but is available in other countries. Limited information indicates that maternal doses of up to 10 mg daily produce low levels in milk and appear to not result in any adverse effects in breastfed infants. Until more data are available, reboxetine should be used with careful monitoring during breastfeeding.
◉ Effects in Breastfed Infants
Four infants whose mothers had postpartum depression had been breastfed (extent not stated) for 1.3 to 2.1 months during maternal reboxetine therapy at an average dose of 6.5 mg (79 mcg/kg) daily. One of the mothers was also taking escitalopram 20 mg daily and another was taking sertraline 300 mg daily. None of the infants exhibited any adverse reactions. Three of the infants had normal Denver developmental scores; the fourth whose mother was taking reboxetine had a developmental age of only 71% of normal, but the problem predated maternal reboxetine therapy.
Five women used reboxetine during pregnancy and lactation (extent not stated) in unspecified doses. No adverse effects were noted in their infants and normal developmental milestones were reported.
◉ Effects on Lactation and Breastmilk
Reboxetine increased serum prolactin in male subjects. The relevance of this finding to nursing mothers is not clear. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 37% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge. The antidepressants used by the mothers were not specified.
A retrospective cohort study of hospital electronic medical records from 2001 to 2008 compared women who had been dispensed an antidepressant during late gestation (n = 575) to those who had a psychiatric illness but did not receive an antidepressant (n = 1552) and mothers who did not have a psychiatric diagnosis (n = 30,535). Women who received an antidepressant were 37% less likely to be breastfeeding at discharge than women without a psychiatric diagnosis, but no less likely to be breastfeeding than untreated mothers with a psychiatric diagnosis. None of the mothers were taking reboxetine.
In a study of 80,882 Norwegian mother-infant pairs from 1999 to 2008, new postpartum antidepressant use was reported by 392 women and 201 reported that they continued antidepressants from pregnancy. Compared with the unexposed comparison group, late pregnancy antidepressant use was associated with a 7% reduced likelihood of breastfeeding initiation, but with no effect on breastfeeding duration or exclusivity. Compared with the unexposed comparison group, new or restarted antidepressant use was associated with a 63% reduced likelihood of predominant, and a 51% reduced likelihood of any breastfeeding at 6 months, as well as a 2.6-fold increased risk of abrupt breastfeeding discontinuation. Specific antidepressants were not mentioned.

[1]. Biol Psychiatry . 2000 May 1;47(9):818-29.

[2]. J Clin Psychiatry . 2002 Jan;63(1):31-7.

[3]. J Clin Psychiatry . 1999 Jun;60(6):400-6.

[4]. Neuropsychopharmacology . 2002 Aug;27(2):237-47.

[5]. J Pharmacol Exp Ther . 2002 Nov;303(2):664-72.

A morpholine derivative that is a selective and potent noradrenaline reuptake inhibitor; it is used in the treatment of DEPRESSIVE DISORDER.

C20H27NO6S

409.5

409.155

C, 58.66; H, 6.65; N, 3.42; O, 23.44; S, 7.83

98769-84-7

Reboxetine; 71620-89-8; (R,R)-Reboxetine mesylate; 105017-39-8

127150

White to off-white solid powder

443.7ºC at 760 mmHg

170-171ºC

188.2ºC

4.107

2

7

6

28

425

2

S(C([H])([H])[H])(=O)(=O)O[H].O1C([H])([H])C([H])([H])N([H])C([H])([H])[C@]1([H])[C@@]([H])(C1C([H])=C([H])C([H])=C([H])C=1[H])OC1=C([H])C([H])=C([H])C([H])=C1OC([H])([H])C([H])([H])[H]

CGTZMJIMMUNLQD-STYNFMPRSA-N

InChI=1S/C19H23NO3.CH4O3S/c1-2-21-16-10-6-7-11-17(16)23-19(15-8-4-3-5-9-15)18-14-20-12-13-22-18;1-5(2,3)4/h3-11,18-20H,2,12-14H2,1H3;1H3,(H,2,3,4)/t18-,19-;/m1./s1

(2R)-2-[(R)-(2-ethoxyphenoxy)-phenylmethyl]morpholine;methanesulfonic acid

PNU 155950E; PNU155950E; PNU-155950E; FCE-20124 mesylate; PNU-155950E mesylate; FCE 20124 mesylate; PNU 155950E mesylate; FCE20124 mesylate; PNU155950E mesylate; Reboxetine mesilate; Reboxetine; Edronax; Reboxetine mesylate; Vestra (TN); AC1L2RIX; AC1Q6WCV; DSSTox_CID_25690; DSSTox_RID_81062; DSSTox_GSID_45690.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 82~125 mg/mL (200.2~305.3 mM)
Water: < 1 mg/mL
Ethanol: ~82 mg/mL (~200.2 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.08 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (5.08 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (5.08 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 110 mg/mL (268.62 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)