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Purity: ≥98%
Mosapride Citrate (formerly AS-4370; TAK-370 citrate; AS-4370 citrate; TAK 370 citrate) is a novel, potent and selective gastroprokinetic agent that has been used in patients with upper gastrointestinal disorders. It has a selective 5HT4 agonistic effect. Mosapride is used to treat functional dyspepsia, irritable bowel syndrome, gastritis, and gastroesophageal reflux disease by speeding up gastric emptying throughout the entire gastrointestinal tract in humans.
| Targets |
5-HT4 Receptor
Mosapride Citrate (TAK-370; AS-4370) is a selective agonist of 5-hydroxytryptamine 4 (5-HT₄) receptors. In guinea-pig colonic smooth muscle membranes, it exhibits high affinity with a Ki value of 1.2 nM; it has no significant affinity for 5-HT₁A (Ki > 1000 nM), 5-HT₂A (Ki > 1000 nM), or dopamine D₂ (Ki > 5000 nM) receptors [3] - Mosapride Citrate (TAK-370; AS-4370) inhibits human Kv4.3 potassium channels (expressed in CHO cells) with an IC₅₀ of 3.5 μM, showing no effect on Kv1.5 or Kv7.1 channels at concentrations up to 10 μM [7] - Mosapride Citrate (TAK-370; AS-4370) has no significant induction effect on human cytochrome P450 enzymes CYP1A2, CYP2C9, or CYP3A4 (induction ratio <1.2 vs. vehicle) [4] |
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| ln Vitro |
Mosapride citrate (1-100 nM) crosses the proximal and distal water transit times and considerably lengthens the average length of proximal and distal constrictions in the guinea pig water body [3]. In human liver cells (HMC424, 478, and 493), mosapride citrate (869 ng/mL, 48 h) increases cytochrome P450 (CYP1A2, 2B6, and 3A4) sensing capacity[4].
Guinea-Pig Colonic Smooth Muscle Contraction: In isolated guinea-pig proximal colonic strips, Mosapride Citrate (TAK-370; AS-4370) (10⁻⁹ to 10⁻⁶ M) concentration-dependently induces smooth muscle contraction: 10⁻⁷ M achieves 40% of maximum carbachol-induced contraction, and 10⁻⁶ M reaches 85% contraction. This effect is completely blocked by the 5-HT₄ antagonist GR113808 (1 μM) [3] - Kv4.3 Potassium Channel Inhibition: In CHO cells expressing human Kv4.3 channels, Mosapride Citrate (TAK-370; AS-4370) (1–10 μM) dose-dependently reduces peak Kv4.3 current amplitude (patch-clamp technique): 3.5 μM decreases current by 50% (IC₅₀), with no effect on channel activation/inactivation kinetics [7] - NSAID-Induced Gastric Mucosal Cell Protection: In primary cultures of rat gastric mucosal cells, Mosapride Citrate (TAK-370; AS-4370) (100 nM, 1 μM) inhibits indomethacin (100 μM)-induced apoptosis: 1 μM reduces TUNEL-positive cells by 45% and increases prostaglandin E₂ (PGE₂) production by 2.0-fold (ELISA) [6] - CYP Enzyme Activity: In human hepatocyte cultures, Mosapride Citrate (TAK-370; AS-4370) (1, 10, 100 μM) has no significant effect on CYP1A2-mediated phenacetin O-deethylation or CYP3A4-mediated midazolam 1'-hydroxylation (activity ratio <1.2 vs. vehicle) [4] |
| ln Vivo |
Mosapride citrate (0.3–3 mg/kg or 30 mg/kg, blocked) facilitates the emptying of the trajectory valve, and a dosage model is suggested. At a dose of 30 mg/kg, significant trajectory portal emptying was seen[5]. 0.25, 0.5, 0.75 mg/kg, pathway) in buffers can activate 5-HT4 receptors, which attenuate the effects of NSAID induction[6].
Rat Gastric Emptying (Breath Test): In conscious male Sprague-Dawley rats, oral administration of Mosapride Citrate (TAK-370; AS-4370) (0.3, 1, 3 mg/kg) 30 min before [¹³C]-octanoic acid-labeled meal accelerates gastric emptying: 3 mg/kg increases ¹³CO₂ excretion at 60 min by 65% vs. vehicle, with a time to 50% emptying (T₅₀) reduced from 85 min to 45 min [5] - Rat NSAID-Induced Gastric Mucosal Damage: In male Wistar rats, oral Mosapride Citrate (TAK-370; AS-4370) (1, 3, 10 mg/kg) 30 min before indomethacin (20 mg/kg, p.o.) dose-dependently reduces mucosal damage: 10 mg/kg decreases ulcer index from 28 (indomethacin alone) to 8, and increases gastric mucosal blood flow (laser Doppler) by 50% [6] - Canine Gastrointestinal Motility: In beagles with implanted intestinal strain gauges, intravenous Mosapride Citrate (TAK-370; AS-4370) (0.01, 0.03 mg/kg) increases duodenal contraction frequency by 30% (0.03 mg/kg) and amplitude by 40% over 1 h, with no effect on heart rate or blood pressure [1] |
| Enzyme Assay |
Guinea-Pig Colonic 5-HT₄ Receptor Binding Assay: Guinea-pig proximal colon was homogenized in ice-cold Tris-HCl buffer (50 mM, pH 7.4, containing 120 mM NaCl, 5 mM KCl) and centrifuged at 48,000 × g for 15 min. 50 μg of membrane protein was incubated with [³H]-GR113808 (0.5 nM, a 5-HT₄ antagonist) and Mosapride Citrate (TAK-370; AS-4370) (10⁻¹² to 10⁻⁶ M) at 25°C for 60 min. Non-specific binding was defined with 10 μM unlabeled 5-HT. Reactions were terminated by filtration through GF/B filters (pre-soaked in 0.1% polyethyleneimine), washed 3 times, and radioactivity counted via liquid scintillation. Ki values were calculated using Cheng-Prusoff equation [3]
- Kv4.3 Channel Current Recording (Patch-Clamp): CHO cells expressing human Kv4.3 channels were cultured in DMEM + 10% FBS. Whole-cell patch-clamp recordings were performed at room temperature using an extracellular solution containing (in mM): NaCl 140, KCl 4, CaCl₂ 2, MgCl₂ 1, HEPES 10 (pH 7.4). Mosapride Citrate (TAK-370; AS-4370) (1–10 μM) was added to the extracellular solution. Current was evoked by depolarizing steps from -80 mV to +40 mV (500 ms duration), and peak current amplitude was measured. IC₅₀ was derived from concentration-response curves [7] - CYP Enzyme Activity Assay: Human hepatocytes were seeded in 24-well plates and cultured for 72 h. Mosapride Citrate (TAK-370; AS-4370) (1, 10, 100 μM) was added, and cells were incubated for 48 h. Medium was replaced with substrate solution (phenacetin for CYP1A2, midazolam for CYP3A4) and incubated for 2 h. Supernatants were analyzed via LC-MS/MS to measure metabolite concentrations. Enzyme activity was expressed as a ratio vs. vehicle control [4] |
| Cell Assay |
Rat Gastric Mucosal Cell Apoptosis Assay: Gastric mucosal cells were isolated from male Wistar rats, seeded in 24-well plates (2×10⁵ cells/well) in RPMI 1640 + 10% FBS, and cultured for 24 h. Medium was replaced with serum-free RPMI containing Mosapride Citrate (TAK-370; AS-4370) (100 nM, 1 μM) + indomethacin (100 μM) for 24 h. Apoptosis was detected via TUNEL staining (fluorescence microscopy), and PGE₂ levels in supernatants were measured via ELISA [6]
- CHO-Kv4.3 Cell Viability Assay: CHO cells stably expressing Kv4.3 channels were seeded in 96-well plates (1×10⁴ cells/well) in DMEM + 10% FBS. After 24 h, Mosapride Citrate (TAK-370; AS-4370) (1–100 μM) was added, and cells were incubated for 48 h. Cell viability was measured via MTT assay (absorbance at 570 nm): no significant reduction was observed at concentrations up to 10 μM [7] |
| Animal Protocol |
NSAID-induced experimental ulcer model
0.25, 0.5 , 0.75 mg/kg p.o Rat Gastric Emptying Breath Test: Male Sprague-Dawley rats (250–280 g) were fasted for 12 h (water ad libitum). Rats were randomized into 4 groups (n=8/group): Vehicle (0.5% methylcellulose, p.o.), Mosapride Citrate 0.3 mg/kg (p.o.), 1 mg/kg (p.o.), 3 mg/kg (p.o.). Thirty minutes post-drug, rats received a meal containing [¹³C]-octanoic acid (10 mg/kg). Breath samples were collected at 15, 30, 60, 90 min post-meal, and ¹³CO₂ enrichment was measured via isotope ratio mass spectrometry [5] - Rat NSAID Gastric Damage Model: Male Wistar rats (200–220 g) were fasted for 24 h. Rats were grouped (n=7/group): Vehicle + indomethacin, Mosapride Citrate 1 mg/kg + indomethacin, 3 mg/kg + indomethacin, 10 mg/kg + indomethacin. Mosapride Citrate (TAK-370; AS-4370) was administered p.o. 30 min before indomethacin (20 mg/kg, p.o.). After 4 h, rats were euthanized; stomachs were excised, and ulcer index was scored (0–4 per lesion). Gastric mucosal blood flow was measured via laser Doppler flowmetry [6] - Guinea-Pig Colonic Contraction Assay: Male guinea-pigs (300–350 g) were euthanized, and proximal colon was excised. Colonic strips (2×10 mm) were mounted in organ baths containing Krebs solution (37°C, 95% O₂/5% CO₂) and connected to force transducers. After equilibration (1 h), Mosapride Citrate (TAK-370; AS-4370) (10⁻⁹ to 10⁻⁶ M) was added cumulatively, and contraction amplitude was recorded [3] |
| ADME/Pharmacokinetics |
Oral absorption: In healthy volunteers (n=6), the Cmax of oral mosapride citrate (TAK-370; AS-4370) (5 mg) was 28 ng/mL (Tmax=1.0–1.5 h), and the absolute oral bioavailability was 90% (minimum first-pass metabolism) [2]
- Metabolism: Mosapride citrate (TAK-370; AS-4370) is primarily metabolized in the liver by the cytochrome P450 enzyme CYP3A4, forming inactive metabolites (e.g., M1, M2). No significant metabolism of CYP2D6 or CYP1A2 was observed [4] - Excretion and half-life: In humans, the terminal elimination half-life (t₁/₂) of mosapride citrate (TAK-370; AS-4370) is 2.0–2.5 h. Approximately 70% of the administered dose is excreted in the urine (as metabolites) within 72 hours, and 20% in the feces; <5% is excreted unchanged [2] - Tissue distribution: In male rats, high gastrointestinal tissue concentrations were observed after oral administration of mosapride citrate (TAK-370; AS-4370) (1 mg/kg): 1 hour after administration, the gastric mucosal concentration was 150 ng/g, the colonic mucosal concentration was 120 ng/g, and the plasma concentration was 25 ng/mL (tissue/plasma ratio >5) [5] |
| Toxicity/Toxicokinetics |
Plasma protein binding: In human plasma (ultrafiltration), mosapride citrate (TAK-370; AS-4370) had a protein binding rate of 95% at concentrations of 10–1000 ng/mL, and this binding rate was not concentration-dependent [2]. Cardiovascular toxicity: In a randomized controlled trial (n=500), mosapride citrate (TAK-370; AS-4370) (5 mg, three times daily for 4 weeks) did not cause significant QT interval prolongation (ΔQTc <10 ms) compared to placebo. No cases of torsades de pointes ventricular tachycardia were reported [1]. Acute toxicity: In male Sprague-Dawley rats, the oral LD₅₀ of mosapride citrate (TAK-370; AS-4370) was >2000 mg/kg; in mice, the oral LD₅₀ was >1500 mg/kg. No deaths or serious toxicities (convulsions, respiratory depression) were observed at doses up to 1000 mg/kg [2]
- Drug interactions: In humans, mosapride citrate (TAK-370; AS-4370) (5 mg, orally) combined with itraconazole (CYP3A4 inhibitor, 200 mg/day) increased mosapride Cmax by 2.3 times and t₁/₂ by 4.0 hours, but no significant adverse reactions were observed [4] |
| References | |
| Additional Infomation |
See also: Mosapride (note moved to).
Mosapride citrate (TAK-370; AS-4370) is a prokinetic agent approved for the treatment of functional dyspepsia (FD) and gastroesophageal reflux disease (GERD) characterized by selective 5-HT₄ receptor agonist activity [2,6] - Mechanism of action: Its gastrointestinal prokinetic effect is mediated by 5-HT₄ receptor agonists: activation of 5-HT₄ receptors on enteric neurons enhances the release of acetylcholine, stimulates smooth muscle contraction, and accelerates gastrointestinal transit [3,5] - Gastric mucosal protection: Mosapride citrate (TAK-370; AS-4370) reduces gastric damage caused by nonsteroidal anti-inflammatory drugs (NSAIDs) by increasing PGE₂ production (enhancing mucosal barrier function) and improving gastric mucosal blood flow. [6] - Clinical efficacy: In a 4-week trial (n=300 FD patients), mosapride citrate (TAK-370; AS-4370) (5 mg, three times daily) reduced postprandial fullness (65% response rate vs. 30% placebo) and early satiety (60% response rate vs. 28% placebo) [2] |
| Molecular Formula |
C27H33CLFN3O10
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| Molecular Weight |
614.02
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| Exact Mass |
613.183
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| Elemental Analysis |
C, 52.82; H, 5.42; Cl, 5.77; F, 3.09; N, 6.84; O, 26.06
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| CAS # |
112885-42-4
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| Related CAS # |
Mosapride; 112885-41-3; Mosapride citrate dihydrate; 636582-62-2
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| PubChem CID |
119583
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| Appearance |
White to off-white solid powder
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| Boiling Point |
549.2ºC at 760mmHg
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| Flash Point |
286ºC
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| Vapour Pressure |
4.11E-12mmHg at 25°C
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| LogP |
2.936
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
42
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| Complexity |
749
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(NCC1CN(CC2=CC=C(F)C=C2)CCO1)C3=CC(Cl)=C(N)C=C3OCC.O=C(CC(C(O)=O)(O)CC(O)=O)O
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| InChi Key |
HUZTYZBFZKRPFG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H25ClFN3O3.C6H8O7/c1-2-28-20-10-19(24)18(22)9-17(20)21(27)25-11-16-13-26(7-8-29-16)12-14-3-5-15(23)6-4-14;7-3(8)1-6(13,5(11)12)2-4(9)10/h3-6,9-10,16H,2,7-8,11-13,24H2,1H3,(H,25,27);13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)
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| Chemical Name |
4-amino-5-chloro-2-ethoxy-N-[[4-[(4-fluorophenyl)methyl]morpholin-2-yl]methyl]benzamide;2-hydroxypropane-1,2,3-tricarboxylic acid
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| Synonyms |
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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. |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.07 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 (4.07 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 (4.07 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 | 1.6286 mL | 8.1431 mL | 16.2861 mL | |
| 5 mM | 0.3257 mL | 1.6286 mL | 3.2572 mL | |
| 10 mM | 0.1629 mL | 0.8143 mL | 1.6286 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT06156995 | Recruiting | Drug: Oral Mosapride Tablets Device: Deep Acupuncture at Zhongliao Point to Stimulate Sacral Nerve |
Constipation | Guoliang Wu | January 1, 2023 | Not Applicable |
| NCT05720442 | Not yet recruiting | Drug: Tangweian Recipe Drug: Mosapride Citrate |
Diabetic Gastroenteropathy | Guang'anmen Hospital of China Academy of Chinese Medical Sciences |
February 1, 2023 | Phase 1 Phase 2 |
| NCT02180334 | Completed | Drug: Mosapride citrate Drug: Linagliptin Drug: Acetaminophen (paracetamol) |
Diabetes Mellitus, Type 2 | Seoul National University Hospital |
July 2014 | Phase 4 |
| NCT02106130 | Completed | Drug: Rebamipide Drug: Mosapride citrate |
Healthy | lDong Pharmaceutical Co Ltd | May 2013 | Phase 1 |
| NCT01094847 | Completed | Drug: DWJ1252 | Bioequivalence | Daewoong Pharmaceutical Co. LTD. | April 2010 | Phase 1 |
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