SSRIs/selective serotonin reuptake inhibitors

Fluvoxamine maleate likewise demonstrates dose-dependent antinociception in the paw pressure test in non-ligated mice. In the acute paw pressure test, fluoxetine maleate also produces an antinociceptive effect that is countered by granisetron, an antagonist of the 5-HT3 receptor.[2] Fluvoxamine (10 and 30 mg/kg, i.p.) dose-dependently increases synaptic efficacy in the hippocampo-mPFC pathway in the rat hippocampo-medial prefrontal cortex (mPFC).[3] In rats under anesthesia, fluvoxamine (10 and 30 mg/kg, i.p.) inhibits long-term potentiation (LTP) in the hippocampal CA1 field. While the 5-HT(4) receptor antagonist GR 113808 (20 mg/rat, i.c.v.) and the 5-HT(7) receptor antagonist DR 4004 (10 mg/rat, i.c.v.) do not completely reverse the suppression of LTP induced by fluvoxamine (30 mg/kg, i.p.), they do.[4] An isolated rat vas deferens cultured in Krebs-Henseleit solution responds to norepinephrine more strongly when fluvoxamine maleate is added. With an IC50 of 18.2μM and 3.99μM, respectively, fluoxetine hydrochloride and fluoxetine maleate inhibit the contraction brought on by potassium ions in the isolated rat uterus preparation.[5]

MTS cell viability assays[4]
Cellular viability was assessed using CellTiter 96 Aqueous One Solution Cell Proliferation Assays. Briefly, SK-N-SH cells were seeded in 96-well plates. Cells were allowed to attach for 24 h. For evaluation of the toxicity of Flv on SK-N-SH cells, cells were treated with 10, 25, 50, 75, or 100 μg/ml Flv for 24 h at 37 °C. For evaluation of the alleviation effect of Flv on Px-induced neurotoxicity, SK-N-SH cells were pre-treated with or without 10 μg/ml Flv for 12 h followed by 1 μM Px treatment with or without 10 μg/ml Flv for 24 h. To confirm the involvement of Sig-1 R in alleviation effect on Px- induced neurotoxicity, SK-N-SH cells were incubated with 1 μM Px, 10 μg/ml Flv and 1 μM NE100 for 24 h. Next, 20 μl of MTS reagent was added to each well and cells were incubated for 2 h. Optical density was measured at 490 nm using a Micro Plate Reader.

---

Western blots[4]
SK-N-SH cells were pre-treated with or without 10 μg/ml Flv for 12 h followed by 1 μM Px treatment with or without 10 μg/ml Flv for 24 h at 37 °C. Cells were washed in Tris-buffered saline (TBS), harvested, and lysed in RIPA buffer with a protease inhibitor cocktail (Roche, Mannheim, Germany), and a phosphatase inhibitor cocktail. Lysates were sonicated on ice three times for five seconds each, and then incubated for 15 min. After centrifugation for 20 min at 13,000 g, supernatants were retained and boiled in SDS sample buffer. Lysates (10 μg) were separated on SDS-polyacrylamide gels and transferred to polyvinylidene fluoride (PVDF) membranes. Non-specific protein binding was blocked by incubating membranes for 1 h at room temperature in 5% w/v non-fat milk powder in TBS-T [50 mM Tris–HCl (pH 7.6), 150 mM NaCl, and 0.1% v/v Tween-20]. The membranes were incubated overnight at 4 °C with the following primary antibodies: anti-CHOP (1:1000), anti-caspase 4 (1:500), anti-caspase 3 (1:1000), anti-sigma 1 receptor (Sig-1R) (1:250) and anti-GAPDH (1:1000). The membranes were then washed three times in TBS-T for 5 min. Finally, the membranes were incubated for 60 min at room temperature with HRP-conjugated anti-rabbit or anti-mouse antibodies. Protein bands were detected using the ECL Plus kit. The intensity of each band was quantified using NIH image J software.

[1]. Psychopharmacology (Berl). 2004 Nov;176(2):195-203.

[2]. Neuropharmacology. 2006 Sep;51(4):866-72.

[3]. Brain Res. 2002 Sep 13;949(1-2):131-8.

[4]. Fluvoxamine alleviates paclitaxel-induced neurotoxicity. Biochem Biophys Rep. 2015 Dec; 4: 202–206./a >

The effects of quetiapine (10 mg/kg) with fluvoxamine (10 mg/kg) on [5-HT]ex and [DA]ex were compared in the rat dorsal striatum, prefrontal cortex, nucleus accumbens (core and shell), and thalamus by means of microdialysis coupled to HPLC with electrochemical detection.[1]

---

There is an association between depression and chronic pain, and some antidepressants exert antinociceptive effects in humans and laboratory animals. We examined the effects of fluvoxamine, a selective serotonin reuptake inhibitor, on mechanical allodynia and its mechanism of action in the mouse chronic pain model, which was prepared by partially ligating the sciatic nerve. The antiallodynic effect was measured using the von Frey test. Fluvoxamine produced antiallodynic effects following both systemic and intrathecal administration. In 5-hydroxytryptamine (5-HT)-depleted mice, prepared by intracerebroventricular injection of 5,7-dihyroxytryptamine, the fluvoxamine-induced antiallodynic effect was significantly attenuated. The antiallodynic effects of systemic fluvoxamine were also reduced by both systemic and intrathecal administration of ketanserin, a 5-HT2A/2C receptor antagonist. In addition, fluvoxamine also induced antinociceptive effect in the acute paw pressure test, and this effect was antagonized by the 5-HT3 receptor antagonist granisetron. These results indicate that fluvoxamine exerts its antiallodynic effects on neuropathic pain via descending 5-HT fibers and spinal 5-HT2A or 5-HT2C receptors, and the antinociception on acute mechanical pain via 5-HT3 receptors.[2]

---

The present studies were conducted to examine the effects of single and repeated treatments with fluvoxamine, which is a selective serotonin reuptake inhibitor (SSRI), on the synaptic efficacy and synaptic plasticity in the rat hippocampo-medial prefrontal cortex (mPFC) pathway in vivo. It has been reported that the projections arising from the hippocampal structures to the mPFC are involved in the execution of higher cognitive functions in rats. The evoked potentials were recorded in the mPFC by stimulation of the CA1/subicular region of the ventral hippocampus in halothane-anesthetized rats. Single administration of fluvoxamine (10 and 30 mg/kg, i.p.) enhanced synaptic efficacy in the hippocampo-mPFC pathway in a dose-dependent manner. Although repeated treatments with fluvoxamine (30 mg/kg, i.p. after 30 mg/kg/dayx21 days, p.o.) caused an enhancement of synaptic efficacy, there was no significant difference between single and repeated treatments. The input/output characteristics showed hypersensitivity to stimulation intensity in the group with repeated fluvoxamine treatments. The establishment of long-term potentiation (LTP) in the hippocampo-mPFC pathway after a single administration of fluvoxamine was not different from that in the saline-injected group. On the other hand, the hippocampo-mPFC LTP was significantly augmented by repeated treatments with fluvoxamine when compared to a single treatment. These findings suggest that the serotonergic system could modulate the synaptic plasticity at hippocampal-mPFC synapses. The present study, furthermore, suggests that the enhancement of LTP in the hippocampo-mPFC pathway produced by repeated treatments with fluvoxamine may be implicated in the SSRI-induced therapeutic effect on psychiatric disorders.[3]

---

C19H25F3N2O6

434.41

434.17

C, 52.53; H, 5.80; F, 13.12; N, 6.45; O, 22.10

61718-82-9

Fluvoxamine; 54739-18-3; (E)-Fluvoxamine-d4 maleate; 1432075-74-5; Fluvoxamine-d4 maleate

White to off-white solid powder

3.61

131.44

COCCCC/C(=N\OCCN)/C1=CC=C(C=C1)C(F)(F)F.C(=C\C(=O)O)\C(=O)O

LFMYNZPAVPMEGP-PIDGMYBPSA-N

InChI=1S/C15H21F3N2O2.C4H4O4/c1-21-10-3-2-4-14(20-22-11-9-19)12-5-7-13(8-6-12)15(16,17)18;5-3(6)1-2-4(7)8/h5-8H,2-4,9-11,19H2,1H3;1-2H,(H,5,6)(H,7,8)/b20-14+;2-1-

(Z)-but-2-enedioic acid;2-[(E)-[5-methoxy-1-[4-(trifluoromethyl)phenyl]pentylidene]amino]oxyethanamine

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.75 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 25.0 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.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (5.75 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 25.0 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.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (5.75 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: 20 mg/mL (46.04 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

---

Solubility in Formulation 5: 20 mg/mL (46.04 mM) in phosphate buffer Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

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