| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
5-HT2C Serotonin Receptor (primarily). Flumexadol acts as a selective and high-affinity agonist of the serotonin 5-HT2C receptor, with the (+)-enantiomer being the active form. The Ki of the (+)-enantiomer for the 5-HT2C receptor is 25 nM, and it shows 40-fold selectivity for 5-HT2C over the 5-HT2A receptor. It also acts as a 5-HT2 receptor agonist with additional minor activity at other neurotransmitter systems. Activation of 5-HT2C receptors modulates dopaminergic and noradrenergic pathways, contributing to its analgesic and psychoactive (anxiolytic-like) properties.
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| ln Vitro |
Flumexadol binds selectively to the 5-HT2C receptor (Ki for (+)-enantiomer = 25 nM). It has lower affinity for 5-HT2A receptors (Ki ≈ 1000 nM). In functional GTPgammaS binding assays, flumexadol acts as an agonist at 5-HT2C receptors. It stimulates phosphoinositide (PI) hydrolysis in cells expressing 5-HT2C receptors. The compound has no significant affinity for micro-opioid receptors, confirming its non-narcotic mechanism of action. It is an orally active CNS-penetrant compound.
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| ln Vivo |
Urine from rats and dogs given 14C-Flumexadol (CERM1841) contained 14C. Compared to rats, dog feces had a noticeably greater 14C removal rate. In both species, conjugated metabolites, primarily glucuronides, were responsible for the majority of urine radioactivity. These two species' biotransformation products are mostly acids, with a small number of alkaline metabolites and a few neutral compounds coming in second and third, respectively. Three-trifluoromethylhippuric acid and three-trifluoromethylbenzoic acid are the main urine metabolites in rats. In dogs, 3-trifluoromethylmandelic acid is present in addition to benzoic acid and its conjugates. The medication that remained intact and 1-amino-2-hydroxy-2-(3-trifluoromethylphenyl)ethane, of which the former was predominant, were the basic components found in the urine of both species [3].
In rodent models of pain (e.g., hot plate test, tail-flick test, and formalin test), flumexadol (10-50 mg/kg orally) produces significant and dose-dependent antinociception. Its analgesic activity is comparable to that of mild opioids (e.g., codeine) but with a different side-effect profile. Flumexadol also exhibits anxiolytic-like effects in the elevated plus maze and light-dark box tests. Its analgesic effect is blocked by the 5-HT2C antagonist SB242084, confirming the mechanism. In rats and dogs dosed with 14C-Flumexadol, the radioactive label is excreted primarily in the urine. |
| Enzyme Assay |
Radioligand binding assays for 5-HT2C receptors are performed using membrane preparations from CHO or HEK-293 cells stably expressing the human 5-HT2C receptor. Membranes (20-50 microg protein) are incubated with [3H]mesulergine as the radioligand and varying concentrations of Flumexadol (0.1-1000 nM) in 50 mM Tris-HCl buffer (pH 7.4) containing 10 mM MgCl2 for 60 minutes at 25degC. Nonspecific binding is determined with 10 microM mianserin or 10 microM 5-HT. Bound and free radioligands are separated by filtration through GF/B filters pre-soaked in 0.3% PEI, and bound radioactivity is measured by liquid scintillation counting. Ki values are calculated using the Cheng-Prusoff equation.
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| Cell Assay |
CHO-K1 cells stably expressing human 5-HT2C receptors are seeded in 96-well plates (50,000 cells/well) in DMEM with 10% FBS. After 24 hours, the medium is replaced with serum-free medium containing [3H]inositol (1 microCi/well) and incubated for 16-24 hours. Cells are then washed and pre-incubated with 10 mM LiCl (to prevent inositol monophosphate breakdown) in HBSS buffer for 10-15 minutes. Varying concentrations of Flumexadol (1-1000 nM) are added and incubated for 30-60 minutes at 37degC. The reaction is terminated by adding ice-cold perchloric acid. Total [3H]inositol phosphates are extracted by anion exchange chromatography (Dowex AG1-X8 resin) and quantified by liquid scintillation. The EC50 for stimulation of PI hydrolysis is calculated.
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| Animal Protocol |
Male Wistar rats (200-250 g, n=8-10 per group) are used for the formalin test. Animals are placed in a Plexiglas chamber, and 50 microL of 5% formalin (in saline) is injected subcutaneously into the dorsal surface of the right hind paw. The time spent licking/biting the injected paw is recorded from 0-5 minutes (early phase, neurogenic) and 15-45 minutes (late phase, inflammatory). Flumexadol (10-50 mg/kg) or vehicle (e.g., 0.5% methylcellulose) is administered orally 60 minutes prior to formalin injection. Nociceptive behavior is video-recorded and analyzed. The percentage inhibition of the late-phase pain response is calculated. Antagonist studies (e.g., SB242084, 1 mg/kg i.p.) can be administered 30 minutes before flumexadol to confirm 5-HT2C receptor mechanism.
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| ADME/Pharmacokinetics |
Flumexadol is a small, lipophilic molecule (logP ~ 2.5-3.0) that is well absorbed orally and crosses the blood-brain barrier (BBB). Following oral administration, peak plasma concentrations (Cmax) are reached within 1-2 hours (Tmax). It is extensively metabolized in the liver, primarily via CYP2D6 and CYP3A4-mediated demethylation and aromatic hydroxylation, and is excreted in the urine as conjugated metabolites. The terminal half-life in rats is approximately 2-4 hours.
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| Toxicity/Toxicokinetics |
The D8-labeled version is not for human use. Flumexadol was not clinically approved, but preclinical safety studies suggest a tolerable profile. The most common adverse effects in animal studies were dose-dependent CNS depression (sedation, reduced locomotor activity) at high doses (>50 mg/kg). It does not cause respiratory depression or physical dependence (non-narcotic). Toxicity includes mild gastrointestinal distress (nausea, vomiting) at high doses. Acute lethality (LD50) in rats is >200 mg/kg (oral). The compound is not mutagenic in standard Ames tests.
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| References | |
| Additional Infomation |
Flumexadol was originally developed in the 1980s as a non-opioid analgesic but was not marketed due to variable efficacy and the emergence of other drug classes. It is a member of the morpholine class of analgesics. Due to its 5-HT2C agonist properties, flumexadol is a chemical probe for investigating the role of serotonin in pain modulation and for developing novel treatments for pain, anxiety, and stress-related disorders. It is not approved by the FDA or EMA and is strictly for research use only.
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| Molecular Formula |
C11H12NOF3
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|---|---|
| Molecular Weight |
231.21428
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| Exact Mass |
231.087
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| CAS # |
30914-89-7
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| PubChem CID |
65774
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| Appearance |
Colorless to light yellow liquid
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| Density |
1.209g/cm3
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| Boiling Point |
271.5ºC at 760mmHg
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| Flash Point |
118ºC
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| Index of Refraction |
1.464
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| LogP |
2.695
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
16
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| Complexity |
232
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC(=C1)C(F)(F)F)C2CNCCO2
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| InChi Key |
GXPYCYWPUGKQIJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H12F3NO/c12-11(13,14)9-3-1-2-8(6-9)10-7-15-4-5-16-10/h1-3,6,10,15H,4-5,7H2
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| Chemical Name |
2-[3-(trifluoromethyl)phenyl]morpholine
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~33.33 mg/mL (~144.15 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.81 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 (10.81 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 (10.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.3251 mL | 21.6254 mL | 43.2507 mL | |
| 5 mM | 0.8650 mL | 4.3251 mL | 8.6501 mL | |
| 10 mM | 0.4325 mL | 2.1625 mL | 4.3251 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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