Trimebutine Maleate (also known as Mebutin) is a potent agonist of peripheral mu, kappa and delta opiate receptors, it is used as spasmolytic agent for treatment of both acute and chronic abdominal pain. The maleic acid salt of trimebutine is marketed under the trademark of Debridat, Recutin, Polybutin, or Modulon for treatment of irritable bowel syndrome and other gastrointestinal disorders. Trimebutine exerts its effects in part due to causing a premature activation of phase III of the migrating motor complex in the digestive tract.
Physicochemical Properties
| Molecular Formula | C26H33NO9MOLECULARWEIGHT |
| Molecular Weight | 503.5415 |
| Exact Mass | 503.215 |
| CAS # | 34140-59-5 |
| Related CAS # | Trimebutine;39133-31-8 |
| PubChem CID | 5388977 |
| Appearance | White to off-white solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 497.8±45.0 °C at 760 mmHg |
| Melting Point | 122-124ºC |
| Flash Point | 254.8±28.7 °C |
| Vapour Pressure | 0.0±2.9 mmHg at 25°C |
| Index of Refraction | 1.610 |
| LogP | 3.61 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 12 |
| Heavy Atom Count | 36 |
| Complexity | 585 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CCC(COC(=O)C1=CC(=C(C(=C1)OC)OC)OC)(C2=CC=CC=C2)N(C)C.C(=C\C(=O)O)\C(=O)O |
| InChi Key | FSRLGULMGJGKGI-BTJKTKAUSA-N |
| InChi Code | InChI=1S/C22H29NO5.C4H4O4/c1-7-22(23(2)3,17-11-9-8-10-12-17)15-28-21(24)16-13-18(25-4)20(27-6)19(14-16)26-5;5-3(6)1-2-4(7)8/h8-14H,7,15H2,1-6H3;1-2H,(H,5,6)(H,7,8)/b;2-1- |
| Chemical Name | (Z)-but-2-enedioic acid;[2-(dimethylamino)-2-phenylbutyl] 3,4,5-trimethoxybenzoate |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vitro | Trimebutine maleate (1–20 μM, 60 h) concurrently inhibits BKCa and calcium channels, which inhibits the development of A2780-SP cells [2]. Astrocytoma/astroblastoma cells' cell viability, migration, and ERK and AKT signaling pathways are all inhibited by trimebutine maleate (10-200 μM, 24-72 h) [3]. |
| ln Vivo | A single dosage of 25–50 mg/kg PO of trimebutine maleate decreases the C57Bl6 electrode's responsiveness to intestinal distension [4]. |
| Cell Assay |
Cell Proliferation Assay[2] Cell Types: A2780-SP cell Tested Concentrations: 1μM, 10μM, 20μM Incubation Duration: 60 hrs (hours) Experimental Results: Dose-dependent inhibition of A2780-SP cell proliferation. Cell migration assay[3] Cell Types: U-87 MG human glioblastoma cells Tested Concentrations: 10 μM, 50 μM, 100 μM, 200 μM Incubation Duration: 24 hrs (hours), 48 hrs (hours), 72 hrs (hours) Experimental Results: Significant gap closure Blocked, the most severe effective inhibition was observed at 200 µM concentration at all time points after 24, 48 and 72 hrs (hours) of incubation. Apoptosis analysis [2] Cell Types: A2780-SP Cell Tested Concentrations: 1 μM, 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Concentrations above 1 μM induce G0/G1 arrest and Dramatically increase the number of AV+/PI+ cells. Western Blot Analysis [2] Cell Types: A2780-SP Cell Tested Concentrations: 1 μM, 10 μM Incubation Duration: 24 h Experimental Results: The expression of OCT3/4 and SOX2 proteins related to stemness was Dramatically diminished, and the ERK phosphorylation related to cell growth was Dramatically diminished. |
| References |
[1]. Effectiveness of trimebutine maleate on modulating intestinal hypercontractility in a mouse model of postinfectious irritable bowel syndrome . European Journal of Pharmacology, 2010, 636(1-3): 159-165. [2]. Repositioning trimebutine maleate as a cancer treatment targeting ovarian cancer stem cells . Cells, 2021, 10(4): 918. [3]. Trimebutine promotes glioma cell apoptosis as a potential anti-tumor agent . Frontiers in Pharmacology, 2018, 9: 664. [4]. A novel orally administered trimebutine compound (GIC‐1001) is anti‐nociceptive and features peripheral opioid agonistic activity and hydrogen sulphide‐releasing capacity in mice . European journal of pain, 2016, 20(5): 723-730. [5]. Lee H T, Kim B J. Trimebutine as a modulator of gastrointestinal motility . Archives of pharmacal research, 2011, 34(6): 861-864. |
| Additional Infomation |
Trimebutine maleate is a trihydroxybenzoic acid. Proposed spasmolytic with possible local anesthetic action used in gastrointestinal disorders. |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~198.59 mM) H2O : ~25 mg/mL (~49.65 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.96 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 (4.96 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (4.96 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9859 mL | 9.9297 mL | 19.8594 mL | |
| 5 mM | 0.3972 mL | 1.9859 mL | 3.9719 mL | |
| 10 mM | 0.1986 mL | 0.9930 mL | 1.9859 mL |