| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
| Targets |
The primary molecular targets of Tofisopam are phosphodiesterase (PDE) isoenzymes, rather than the GABA-A receptor benzodiazepine binding site. It acts as an isoenzyme-selective PDE inhibitor with the highest affinity for PDE-4A1 (IC50 = 0.42 μM), followed by PDE-10A1 (IC50 = 0.92 μM), PDE-3A (IC50 = 1.98 μM), and PDE-2A3 (IC50 = 2.11 μM). Tofisopam does not bind significantly to the classical benzodiazepine site on the GABA-A receptor, distinguishing its mechanism from that of 1,4-benzodiazepines. The S-enantiomer is reported to be approximately ten times more active than the R-enantiomer.
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| ln Vitro |
When given at a dose of 50 mg/kg for seven days in a row, tofisopam can help amnesic rats with their impaired cognitive function, as well as reduce synaptic transmission in the hippocampus, promote the growth of subgranular zones, and strengthen the astrocytes in the rats. the decrease in cells with cytoplasm [1].
Tofisopam inhibits phosphodiesterase isoenzyme activity in cell-free enzymatic assays, with IC50 values of 2.11 μM for PDE-2A3, 1.98 μM for PDE-3A, 0.42 μM for PDE-4A1, and 0.92 μM for PDE-10A1. It has been shown to increase cAMP activity in vitro. In human recombinant CYP3A4 supersome assays, Tofisopam demonstrated inhibitory effects on CYP3A4 enzyme activity, though its potency was approximately one order of magnitude lower than that of the potent CYP3A4 inhibitor ketoconazole. The compound also exhibits in vitro anti-inflammatory and immunomodulatory effects. |
| ln Vivo |
Tofisopam (50 mg/kg, i.p., twice daily, 5 days/week for 19 days) was effective in a mouse model of negative symptoms of psychosis. Oral administration of Tofisopam at 30 and 100 mg/kg significantly inhibited water-immersion stress-induced gastric ulceration in normal rats in a dose-dependent manner. In scopolamine-induced amnesic rats, Tofisopam at 50 mg/kg for seven days improved cognitive performance, enhanced hippocampal synaptic transmission, increased proliferation in subgranular zones, and reversed the decrease in astrocytes. In mice, Tofisopam (50 and 100 mg/kg) significantly shortened immobility time in tail suspension and forced swimming tests. However, Tofisopam showed no anxiolytic effect in animal models (social interaction test and punished drinking test at 10–50 mg/kg) that are sensitive to 1,4-benzodiazepines.
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| Enzyme Assay |
In vitro PDE inhibition assays are typically performed using recombinant human PDE isoenzymes incubated with varying concentrations of Tofisopam and a fluorescent or radioactive substrate, with IC50 values determined from dose-response curves. For CYP3A4 inhibition studies, human recombinant CYP3A4 supersomes are incubated with Tofisopam and a specific substrate, and metabolite formation is measured via LC-MS/MS, with ketoconazole used as a positive control. Receptor binding studies for the GABA-A benzodiazepine site are conducted using radioligand binding assays with membrane preparations from rat brain or recombinant receptors, where Tofisopam is tested for displacement of [³H]flunitrazepam or similar ligands.
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| Cell Assay |
In vitro cellular assays for Tofisopam typically employ cell lines such as neuronal or immune cells to assess PDE inhibition and downstream cAMP accumulation. Cells are treated with Tofisopam at various concentrations for defined periods, and intracellular cAMP levels are measured using competitive ELISA or HTRF-based assays. For anti-inflammatory and immunomodulatory assessments, cells are stimulated with inflammatory mediators (e.g., LPS) in the presence or absence of Tofisopam, and cytokine production is quantified by ELISA. CYP3A4 inhibition is evaluated using human recombinant CYP3A4 supersomes incubated with Tofisopam and a probe substrate, with metabolite formation monitored by LC-MS.
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| Animal Protocol |
Tofisopam is administered orally in animal studies, typically dissolved in suitable vehicles such as 0.5% carboxymethylcellulose or saline. In the water-immersion stress-induced gastric ulcer model, rats receive Tofisopam at 30 and 100 mg/kg orally 30–60 minutes prior to stress exposure, and gastric lesions are subsequently scored. In the mouse model of negative symptoms of psychosis, Tofisopam is administered intraperitoneally at 50 mg/kg twice daily. In cognitive impairment studies using scopolamine-induced amnesic rats, Tofisopam is given at 50 mg/kg orally for seven consecutive days, followed by behavioral tests (e.g., Morris water maze, passive avoidance) and histological analysis of hippocampal tissue.
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| ADME/Pharmacokinetics |
Metabolism / Metabolites
Liver metabolism. Biological half-life 6-8 hours Tofisopam is rapidly and almost completely absorbed from the gastrointestinal tract after oral administration. Peak plasma concentrations (Cmax) are achieved within 1–2 hours. The plasma concentration then declines monoexponentially with an elimination half-life of approximately 6–8 hours. Steady state is reached within 3 days of regular administration. Approximately 50% of Tofisopam binds to plasma proteins. The drug is primarily metabolized in the liver via demethylation and other cytochrome P450-mediated pathways. It is mainly excreted in urine (60–80%) and does not accumulate in the body with repeated dosing. |
| Toxicity/Toxicokinetics |
Tofisopam is generally well tolerated, with a side-effect profile distinct from classical benzodiazepines. Reported adverse effects include loss of appetite, dry mouth, nausea, constipation, headache, insomnia, restlessness, irritability, and muscle tension. Overdose may cause nausea, vomiting, abdominal pain, and weakness. Tofisopam may potentiate the effects of other CNS depressants and is not recommended for chronic psychosis or obsessive-compulsive/phobic disorders due to a potential increased risk of suicide or aggressive behavior. It can cross the placenta; animal studies do not indicate direct reproductive toxicity, but use during the first trimester of pregnancy is generally advised against as a precaution. The compound is classified as harmful if swallowed and very toxic to aquatic life with long-lasting effects.
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| References | |
| Additional Infomation |
Tofiloxam is an organic molecular entity. Tofiloxam (trade names: Emandaxin and Grandaxin) is a 2,3-benzodiazepine, belonging to the benzodiazepine derivative class. Unlike classic 1,4-benzodiazepines, this compound does not bind to the benzodiazepine binding site of the γ-aminobutyric acid (GABA) receptor, and its psychopharmacological properties also differ from those of this class of compounds. Although tofiloxam is not approved for sale in North America, it is approved for use in several countries worldwide, including parts of Europe. Its D-enantiomer (dexfexam) is currently undergoing a Phase II clinical trial in the United States for the treatment of irritable bowel syndrome. Indications: For the treatment of anxiety disorders and alcohol withdrawal symptoms. Mechanism of Action: Tofiloxam does not bind to the benzodiazepine binding site of the GABA receptor. A study (Rundfeldt C. et al.) showed that tolfoxopam, as an isoenzyme-selective inhibitor of phosphodiesterase (PDE), has the highest affinity for PDE-4A1 (0.42 μM), followed by PDE-10A1 (0.92 μM), PDE-3 (1.98 μM), and PDE-2A3 (2.11 μM).
Tofisopam was first approved in Hungary in January 1975. While not approved in North America, it is approved in various European and Asian countries. The D-enantiomer, dextofisopam, has been investigated in Phase II clinical trials in the U.S. for irritable bowel syndrome and other indications. In a double-blind, placebo-controlled trial, Tofisopam demonstrated significant anxiolytic efficacy comparable to diazepam on the Hamilton Anxiety Rating Scale. Another study found Tofisopam to be equally effective to lorazepam in reducing anxiety with superior tolerability. Tofisopam has also been explored for cognitive enhancement and the treatment of functional dyspepsia and irritable bowel syndrome. Its chemical structure is 5H-2,3-benzodiazepine with molecular formula C₂₂H₂₆N₂O₄ and molecular weight 382.45. |
| Molecular Formula |
C22H26N2O4
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| Molecular Weight |
382.4528
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| Exact Mass |
565.226
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| CAS # |
22345-47-7
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| PubChem CID |
5502
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
479.0±45.0 °C at 760 mmHg
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| Melting Point |
155-159ºC
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| Flash Point |
195.2±21.2 °C
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| Vapour Pressure |
0.0±1.2 mmHg at 25°C
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| Index of Refraction |
1.558
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| LogP |
2.39
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
28
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| Complexity |
579
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCC1C(=NN=C(C2=CC(=C(C=C2)OC)OC)C3=CC(=C(C=C13)OC)OC)C
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| InChi Key |
RUJBDQSFYCKFAA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H26N2O4/c1-7-15-13(2)23-24-22(14-8-9-18(25-3)19(10-14)26-4)17-12-21(28-6)20(27-5)11-16(15)17/h8-12,15H,7H2,1-6H3
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| Chemical Name |
1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine
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| Synonyms |
Tofisopam EGYT-341EGYT341 Emandaxin, Grandaxin, Sériel
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.6147 mL | 13.0736 mL | 26.1472 mL | |
| 5 mM | 0.5229 mL | 2.6147 mL | 5.2294 mL | |
| 10 mM | 0.2615 mL | 1.3074 mL | 2.6147 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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