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Purity: ≥98%
Mizolastine (Mizollen; SL 85.0324; Mistalin; SL-850324; SL 850324; Mistamine; Mizolastina) is a histamine H1-receptor antagonist with anti-allergic effects. It has been used to treat hay fever (seasonal allergic rhinitis), hives, and other allergic reactions. It inhibits the histamine H1-receptor with an IC50 of 47 nM. A single daily dose of non-sedating antihistamine is mizolastine. It usually acts quickly and blocks H1 receptors. Just the binding of histamine to receptors is inhibited; mast cell release of histamine is not stopped. Tight lips and throat are possible side effects.
| Targets |
Histamine H1 receptor ( IC50 = 47 nM )
Histamine H1 receptor (H1R) (human H1R, Ki=0.4 nM; rat H1R, Ki=0.6 nM) [3] |
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| ln Vitro |
Mizolastine (1–10,000 nM; 0.5–6 h) inhibits the release of VEGF, KC, and TNF-α in mast cells[1].
Mizolastine (0.1 µM; 4 h) dramatically lowers the expression of KC, TNF-α, VEGF165, and VEGF120 mRNA in mast cells[1]. Mouse bone marrow-derived mast cells (BMMCs) stimulated with anti-IgE (1 μg/mL) were treated with Mizolastine (SL 850324) (0.1 μM-10 μM). It dose-dependently inhibited VEGF, TNF-α, and keratinocyte-derived chemokine (KC) secretion, with 62% inhibition of TNF-α, 58% of VEGF, and 65% of KC at 10 μM [1] - Radioligand binding assay with human H1R-expressing HEK293 cell membranes showed Mizolastine (SL 850324) competitively bound to H1R, displacing [3H]-pyrilamine with high affinity (Ki=0.4 nM) [3] - Isolated guinea pig ileum smooth muscle strips pre-contracted with histamine (1 μM) were treated with Mizolastine (SL 850324) (0.01 μM-10 μM). It induced concentration-dependent relaxation, EC50=0.8 μM, confirming H1R antagonistic activity [3] |
| ln Vivo |
Mizolastine (0.3 mg/kg; p.o.; once daily for 7 days) suppresses expression of 5-LOX, cytosolic PLA2 (cPLA2), 5-LOX-activating protein, and LTB4 receptor mRNA. It also inhibits production of the 5-LOX AA (arachidonic acid) metabolite leukotriene B4 (LTB4) in the AA-induced inflammation model[2].
Guinea pig allergic rhinitis model: Intranasal administration of Mizolastine (SL 850324) (1 mg/kg, 2 mg/kg) twice daily for 7 days dose-dependently reduced nasal symptoms (sneezing, rhinorrhea) by 55% and 70% respectively, compared to vehicle. It also decreased nasal mucosal eosinophil infiltration by 60% (2 mg/kg dose) [3] - Clinical trial in patients with allergic rhinitis: Oral administration of Mizolastine (SL 850324) (10 mg once daily) for 4 weeks reduced total nasal symptom score (TNSS) by 65% and improved quality of life by 58% compared to placebo [3] - Clinical trial in patients with chronic idiopathic urticaria: Oral Mizolastine (SL 850324) (10 mg once daily) for 6 weeks reduced urticarial lesion number and pruritus score by 72% and 68% respectively [3] |
| Enzyme Assay |
H1R binding assay: Prepare membrane fractions from HEK293 cells expressing human/rat H1R or guinea pig brain tissue. Incubate membranes with [3H]-pyrilamine (0.5 nM) and various concentrations of Mizolastine (SL 850324) (0.001 nM-100 nM) at 25°C for 60 minutes. Separate bound and free ligand by vacuum filtration through glass fiber filters. Measure radioactivity with a liquid scintillation counter and calculate Ki values using the Cheng-Prusoff equation [3]
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| Cell Assay |
Cell Line: Mast cells (from Kunming mice)
Concentration: 1-10000 nM Incubation Time: 0.5-6 h Result: Markedly inhibited release of KC, VEGF and TNF-α in a time- and dose- dependent manner. Mouse mast cell cytokine secretion assay: Isolate bone marrow from BALB/c mice, differentiate into BMMCs in culture medium for 4 weeks. Seed BMMCs in 24-well plates and pre-treat with Mizolastine (SL 850324) (0.1 μM-10 μM) for 30 minutes. Stimulate with anti-IgE (1 μg/mL) for 24 hours. Collect supernatant and quantify VEGF, TNF-α, and KC via ELISA [1] - Guinea pig ileum smooth muscle relaxation assay: Isolate guinea pig ileum segments, mount in organ baths with oxygenated Krebs-Ringer solution (37°C, 95% O2/5% CO2), and equilibrate for 60 minutes. Pre-contract with histamine (1 μM), then add Mizolastine (SL 850324) (0.01 μM-10 μM) cumulatively and record tension changes [3] |
| Animal Protocol |
Male Sprague-Dawley rats (specific-pathogen-free; 234-254 g; 7 to 8-week-old; rat paw edema model)
0.3 mg/kg Oral gavage; single daily for 7 days. Guinea pig allergic rhinitis model: Male Hartley guinea pigs (300-350 g) were sensitized with ovalbumin (100 μg) + aluminum hydroxide (2 mg) via intraperitoneal injection on days 0 and 7. On day 14, intranasal ovalbumin (1% solution) was administered to induce allergic rhinitis. Mizolastine (SL 850324) was dissolved in physiological saline and administered intranasally (1 mg/kg, 2 mg/kg) twice daily for 7 days. Record sneezing and rhinorrhea frequency; collect nasal mucosal tissues for eosinophil counting [3] |
| ADME/Pharmacokinetics |
Absorption: The oral bioavailability in the human body is 90-95%; the peak plasma concentration (Cmax) is reached 1.5-2 hours after oral administration (10 mg dose: Cmax = 280 ng/mL) [3] - Distribution: The volume of distribution (Vd) in the human body is 1.2 L/kg; the brain/plasma concentration ratio is <0.02, indicating that the blood-brain barrier penetration is negligible [3] - Metabolism: It is mainly metabolized in the liver by cytochrome P450 (CYP) 3A4 into inactive metabolites [3] - Excretion: 80% of the dose is excreted in feces (65% as metabolites and 15% as the original drug), and 15% is excreted in urine. The elimination half-life (t1/2) in the human body is 10-12 hours [3]
- Plasma protein binding rate:Mizolastine (SL 850324) has a plasma protein binding rate of 98% in human plasma [3] |
| Toxicity/Toxicokinetics |
Acute toxicity: LD50 in rats and mice > 2000 mg/kg (oral); no deaths or serious clinical symptoms were reported [3] - Chronic toxicity: No significant hepatotoxicity or hematologic abnormalities were observed in rats after oral administration of mizolastine (SL 850324) (100 mg/kg/day) for 6 consecutive months [3] - Clinical side effects: Mild headache (2-3% of patients), fatigue (1-2%) and dry mouth (1%) have been reported. No sedation or cognitive impairment was observed at therapeutic doses [3] - Drug interactions: Concomitant use with CYP3A4 inhibitors (e.g., ketoconazole) increased plasma mizolastine concentration by 30%; no significant interactions were observed with other antihistamines or central nervous system drugs [3]
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| References |
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| Additional Infomation |
Mizolastine belongs to the benzimidazole class of drugs. Mizolastine is currently undergoing clinical trials NCT01928316 (a bioequivalence study comparing domestically produced (Made in China) and imported mizolastine tablets in healthy volunteers). Mizolastine (SL 850324) is a second-generation non-sedating histamine H1 receptor antagonist with anti-allergic and anti-inflammatory activity [1,3]. Its core mechanisms include competitive H1R antagonism (blocking histamine-mediated allergic reactions) and inhibition of mast cell secretion of pro-inflammatory cytokines (TNF-α, VEGF, KC) [1,3]. Indications include allergic rhinitis and chronic idiopathic urticaria, which can relieve symptoms such as sneezing, runny nose, itching and urticaria lesions. [3] Its extremely low blood-brain barrier penetration means it does not have a sedative effect, which distinguishes it from first-generation H1 receptor antagonists. [3]
High oral bioavailability and a long elimination half-life (10-12 hours) support once-daily dosing in adults (10 mg per dose). [3] Its efficacy is comparable to other second-generation antihistamines (e.g., loratadine), but it has a higher safety profile due to minimal off-target effects. [1,3] |
| Molecular Formula |
C24H25FN6O
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| Molecular Weight |
432.49
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| Exact Mass |
432.207
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| Elemental Analysis |
C, 66.65; H, 5.83; F, 4.39; N, 19.43; O, 3.70
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| CAS # |
108612-45-9
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| Related CAS # |
Mizolastine dihydrochloride;1056596-82-7;Mizolastine-13C,d3
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| PubChem CID |
65906
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Melting Point |
217°
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| Index of Refraction |
1.682
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| LogP |
3.42
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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 |
5
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| Heavy Atom Count |
32
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| Complexity |
728
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])N1C2=C([H])C([H])=C([H])C([H])=C2N=C1N1C([H])([H])C([H])([H])C([H])(C([H])([H])C1([H])[H])N(C1=NC([H])=C([H])C(N1[H])=O)C([H])([H])[H]
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| InChi Key |
PVLJETXTTWAYEW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H25FN6O/c1-29(23-26-13-10-22(32)28-23)19-11-14-30(15-12-19)24-27-20-4-2-3-5-21(20)31(24)16-17-6-8-18(25)9-7-17/h2-10,13,19H,11-12,14-16H2,1H3,(H,26,28,32)
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| Chemical Name |
2-[[1-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]piperidin-4-yl]-methylamino]-1H-pyrimidin-6-one
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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 |
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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 (5.78 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 (5.78 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 (5.78 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 | 2.3122 mL | 11.5610 mL | 23.1219 mL | |
| 5 mM | 0.4624 mL | 2.3122 mL | 4.6244 mL | |
| 10 mM | 0.2312 mL | 1.1561 mL | 2.3122 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 |
| NCT01928316 | Completed | Drug: Mizolastine (imported) Drug: Mizolastine domestic (made in China) |
Healthy | Xian-Janssen Pharmaceutical Ltd. | June 2009 | Phase 1 |
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