| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
5-HT2B Receptor 11.2 nM (Ki) 5-HT2C Receptor 324 nM (Ki) 5-HT2A Receptor 1516 nM (Ki)
(+)-Norfenfluramine hydrochloride targets serotonin receptors, specifically 5-HT2A, 5-HT2B, and 5-HT2C. It is a selective 5-HT2B receptor agonist with a Ki of 11.2 nM. It exhibits higher potency than fenfluramine in activating these receptors, which is critical in understanding its effects on mood and appetite regulation. The compound is also more potent than fenfluramine at inducing dopamine release, suggesting additional effects on dopaminergic signaling. |
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| ln Vitro |
Rats' aorta and mesenteric resistance arteries, which have a sharply decreased threshold, are contracted by (+)-norfenfluramine hydrochloride (1 nM to 100 μM)[1]. Rat tissues with normotensive and hypertension conditions exhibit aortic contraction in response to (+)-norfenfluramine hydrochloride (1 and 10 μM, 3 min)[1]. 5-HT release from rat hippocampus synaptosomes is induced by (+)-Norfenfluramine (0-10 μM, 3 min) hydrochloride in a Ca2+-dependent manner [2].
In vitro, (+)-Norfenfluramine hydrochloride acts as a selective 5-HT2B receptor agonist. Its activity is typically assessed by measuring its ability to stimulate calcium mobilization or inositol phosphate accumulation in cells expressing 5-HT2B receptors. The compound shows higher potency than fenfluramine at inducing dopamine release, which may contribute to its effects on reward and motivation. Standard in vitro assays include receptor binding studies, functional assays measuring calcium signaling, and dopamine release assays in synaptosomal preparations. |
| ln Vivo |
In conscious SHAM and DOCA-salt rats, (+)-Norfenfluramine (1-300 μg/kg, iv) hydrochloride causes a pressor response[1]. Rat telencephalon and brainstem 5-HT and 5-HIAA levels are decreased by (+)-Norfenfluramine hydrochloride (2.5 and 5 mg/kg, ip)[3].
In vivo, (+)-Norfenfluramine hydrochloride is primarily responsible for the anorexic effect of fenfluramine. As a 5-HT2B receptor agonist, it modulates serotonergic signaling pathways involved in appetite regulation. The compound also contributes to the side effects of fenfluramine, which may include cardiovascular effects related to 5-HT2B receptor activation. Its higher potency at inducing dopamine release suggests it may also affect reward pathways. The compound is used in research to study the pharmacological effects of fenfluramine metabolites. |
| Enzyme Assay |
For non-cell-based receptor binding assays, (+)-Norfenfluramine hydrochloride can be evaluated using membrane preparations from cells expressing human 5-HT2A, 5-HT2B, or 5-HT2C receptors. Radioligand binding displacement experiments are performed using suitable radiolabeled ligands such as [3H]-ketanserin for 5-HT2A or [3H]-mesulergine for 5-HT2C. Membrane homogenates are incubated with increasing concentrations of the test compound and a fixed concentration of the radioligand at room temperature for 60-90 minutes. Bound radioligand is separated from free by rapid filtration through glass fiber filters. Non-specific binding is determined in the presence of excess unlabeled ligand. Ki values are calculated from displacement curves using nonlinear regression analysis.
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| Cell Assay |
For in vitro cellular assays, cells expressing human 5-HT2B receptors are cultured in appropriate media. For functional assays, intracellular calcium mobilization is measured using fluorescent calcium indicators such as Fluo-4 AM. Cells are loaded with the dye and treated with various concentrations of (+)-Norfenfluramine hydrochloride. Fluorescence intensity is measured using a fluorescence plate reader. The increase in calcium signal compared to control wells indicates agonist activity. EC50 values are calculated from dose-response curves. For dopamine release assays, synaptosomal preparations or cell cultures are treated with the compound, and dopamine release is measured using HPLC or electrochemical detection.
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| Animal Protocol |
Animal/Disease Models: Conscious SHAM and DOCA-salt rats[1].
Doses: 1-300 μg/kg Route of Administration: intravenous (iv) injection (iv), given in a cumulative fashion at 6-min intervals. Experimental Results: Induced pressor response in conscious SHAM and DOCA-salt rats. (change in mean arterial blood pressure at 300 μg/kg, mm Hg, SHAM vehicle=36, SHAM ketanserin=7, DOCA= 51, DOCA ketanserin=19). For in vivo animal studies, (+)-Norfenfluramine hydrochloride can be administered to rodents via intraperitoneal injection. In models of appetite regulation, food intake and body weight are monitored following compound administration. In models of serotonin syndrome or side effect assessment, behavioral and physiological parameters are evaluated. Dosing regimens vary depending on the specific model and desired exposure levels. Blood and tissue samples may be collected for pharmacokinetic analysis. |
| ADME/Pharmacokinetics |
(+)-Norfenfluramine hydrochloride has a molecular weight of 239.67 and a molecular formula of C10H12F3N·HCl. It is supplied with a purity of ≥98%. The compound is soluble in water at ≥10 mg/mL. It should be stored as a powder at -20°C for up to 3 years or at 4°C for up to 2 years. It is for research use only and is not intended for human consumption.
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| Toxicity/Toxicokinetics |
The toxicity profile of (+)-Norfenfluramine hydrochloride is related to its role as a metabolite of fenfluramine. 5-HT2B receptor agonists have been associated with valvular heart disease, which is a known side effect of fenfluramine and related compounds. The compound is for research use only and is not intended for human consumption. Standard toxicological evaluation would include assessment of cardiovascular effects, particularly on heart valve function, as well as effects on the central nervous system.
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| References |
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| Additional Infomation |
(+)-Norfenfluramine hydrochloride (CAS 37936-89-3) is the major hepatic metabolite of (+)-fenfluramine and is primarily responsible for the anorexic effect as well as side effects. It is a selective 5-HT2B receptor agonist with a Ki of 11.2 nM and exhibits higher potency than fenfluramine at inducing dopamine release. It acts as an agonist for serotonin receptors 5-HT2A, 5-HT2B, and 5-HT2C. It is available for research purposes only.
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| Molecular Formula |
C10H13CLF3N
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|---|---|
| Molecular Weight |
239.67
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| Exact Mass |
239.069
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| CAS # |
37936-89-3
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| Related CAS # |
(+)-Norfenfluramine;19036-73-8
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| PubChem CID |
71311600
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| Appearance |
White to off-white solid powder
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| LogP |
4.097
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
15
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| Complexity |
179
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@@H](CC1=CC(=CC=C1)C(F)(F)F)N.Cl
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| InChi Key |
PIDLOFBRTWNFAR-FJXQXJEOSA-N
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| InChi Code |
InChI=1S/C10H12F3N.ClH/c1-7(14)5-8-3-2-4-9(6-8)10(11,12)13;/h2-4,6-7H,5,14H2,1H3;1H/t7-;/m0./s1
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| Chemical Name |
(2S)-1-[3-(trifluoromethyl)phenyl]propan-2-amine;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
H2O: 18.75 mg/mL (78.23 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.1724 mL | 20.8620 mL | 41.7240 mL | |
| 5 mM | 0.8345 mL | 4.1724 mL | 8.3448 mL | |
| 10 mM | 0.4172 mL | 2.0862 mL | 4.1724 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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