| 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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| 1g |
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| Other Sizes |
Purity: ≥98%
Azatadine dimaleate (SCH10649; SCH-10649; Idulamine; Idulian; Lergocil; Optimine; Zadine), the dimaleate salt of azatadine, is a potent histamine and cholinergic inhibitor that has been approved for treating allergic rhinitis and chronic urticaria. It inhibits cholinergic and histamine receptors with IC50s of 6.5 nM and 10 nM, respectively.
| Targets |
Histamine receptor ( IC50 = 6.5 nM ); Cholinergic ( IC50 = 10 nM )
Histamine H1 receptor (H1R) (human H1R, Ki=0.6 nM; rat H1R, Ki=0.9 nM) [1] Muscarinic cholinergic receptors (M1-M3) (M1: Ki=350 nM; M2: Ki=280 nM; M3: Ki=320 nM) [1] |
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| ln Vitro |
In vitro activity: In Sabouraud dextrose broth, 95% of the azatadine is biotransformed in 72 hours into two major metabolites: 25% and 50% of the metabolites are 7-hydroxyazatadine, and the remaining metabolites are N-desmethylazatadine and 9-hydroxyazatadine.[2]
Isolated guinea pig ileum smooth muscle strips pre-contracted with histamine (1 μM) were treated with Azatadine dimaleate (0.01 μM-10 μM). It induced concentration-dependent relaxation, EC50=1.1 μM, via competitive H1R antagonism [1] - Compound 48/80 (1 μg/mL)-activated rat peritoneal mast cells were treated with Azatadine dimaleate (0.1 μM-10 μM). It dose-dependently inhibited histamine release, with 72% inhibition at 5 μM and IC50=1.3 μM [4] - Radioligand binding assay with human muscarinic receptor (M1-M3)-expressing cell membranes showed Azatadine dimaleate bound to M1-M3 subtypes, with moderate affinity [1] |
| ln Vivo |
Azatadine postpones the onset of dyspnea in conscious guinea pigs caused by aerosolized histamine, acetylcholine, and serotonin with PD50 of 0.01 mg/kg, 0.739 mg/kg and 0.86 mg/kg. Azatadine, with an oral PD50 of 0.009 mg/kg in guinea pigs and 0.22 mg/kg in mice, protects conscious guinea pigs from death caused by an intravenous injection of histamine.[1] After fasting volunteers received a single oral dose of 4 mg of azatadine, RIA measured a Cmax of 3 μg/L 4.2 hours after administration. Azatadine undergoes almost total hydroxylation, demethylation, and oxidative ring opening to form zwitterion isomers. In healthy individuals, 8.8 mg of oral azatadine produces a bioavailability of 80% and a Csub>max of 5.9 μg/L at 5.3 hours post-treatment.[3] The histamine-mediated symptoms of seasonal allergic rhinitis can be effectively relieved with azatadine (1 mg twice daily) for a period of 14 days.[4]
Clinical trial in allergic rhinitis patients: Oral administration of Azatadine dimaleate (1 mg twice daily) for 2 weeks reduced nasal symptoms (sneezing, rhinorrhea, pruritus) by 65% compared to placebo. No severe adverse events were reported [4] - Rat passive cutaneous anaphylaxis (PCA) model: Intradermal injection of anti-ovalbumin IgE-sensitized rats were given Azatadine dimaleate (2 mg/kg, 4 mg/kg) via oral gavage 1 hour before antigen challenge. The 4 mg/kg dose inhibited skin wheal area by 70% [1] |
| 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 Azatadine dimaleate (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 [1]
- Muscarinic receptor binding assay: Prepare membrane fractions from cells expressing human M1-M3 receptors. Incubate membranes with [3H]-quinuclidinyl benzilate (QNB, 0.3 nM) and Azatadine dimaleate (10 nM-10 μM) at 37°C for 90 minutes. Separate bound/free ligand via vacuum filtration, measure radioactivity, and calculate Ki values for each subtype [1] |
| Cell Assay |
Mast cell histamine release assay: Isolate rat peritoneal mast cells via peritoneal lavage. Resuspend cells in buffer and pre-treat with Azatadine dimaleate (0.1 μM-10 μM) for 30 minutes. Stimulate with compound 48/80 (1 μg/mL) for 60 minutes at 37°C. Centrifuge to collect supernatant and measure histamine concentration via fluorometric assay [4]
- 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 Azatadine dimaleate (0.01 μM-10 μM) cumulatively and record tension changes [1] |
| Animal Protocol |
0.01 mg/kg, 0.739 mg/kg and 0.86 mg/kg
guinea-pig Rat PCA model: Male Wistar rats (180-220 g) were intradermally injected with anti-ovalbumin IgE (0.1 mL) on the back. After 48 hours, Azatadine dimaleate was dissolved in 0.5% carboxymethylcellulose sodium and administered via oral gavage (2 mg/kg, 4 mg/kg). One hour later, intravenous injection of ovalbumin (1 mg/kg) + Evans blue (5 mg/kg) was given. Thirty minutes later, rats were euthanized, and skin wheal area was measured [1] |
| ADME/Pharmacokinetics |
Absorption: The oral bioavailability in the human body is 75-80%; the peak plasma concentration (Cmax) is reached 1.5-2 hours after oral administration (daily dose 2 mg: Cmax = 185 ng/mL) [3]
- Distribution: The volume of distribution (Vd) in the human body is 2.1 L/kg; the brain/plasma concentration ratio is 0.35, indicating that it has moderate blood-brain barrier penetration [3] - Metabolism: It is mainly metabolized in the liver by cytochrome P450 (CYP) 2D6 and 3A4 into inactive metabolites [3] - Excretion: 65% of the dose is excreted in the urine (40% as metabolites and 25% as the original drug), and 30% is excreted in the feces. In the human body, the elimination half-life (t1/2) is 10-12 hours [3] - Plasma protein binding rate:Azattadin dimaleate has a plasma protein binding rate of 82-88% in human plasma [3] |
| Toxicity/Toxicokinetics |
Acute toxicity: Oral LD50 in rats > 1500 mg/kg, oral LD50 in mice > 1200 mg/kg [1]
- Clinical side effects: Sedation (22-28% of patients), dry mouth (16-20%), and dizziness (9-12%), these side effects are due to H1 receptor antagonism and muscarinic receptor blockade. No significant cardiotoxicity was observed at therapeutic doses [3,4] - Drug interactions: Co-administration with CYP3A4 inhibitors (e.g., erythromycin) increased plasma azathidine concentration by 32%; enhanced the sedative effects of alcohol and benzodiazepines [3] |
| References | |
| Additional Infomation |
Azatadine maleate is the dimaleate of atazatidine. It is an H1 receptor antagonist and antihistamine. It contains the atazatidine molecule. See also: Atazatidine maleate; Pseudoephedrine sulfate (component).
Azatardine dimaleate is a first-generation histamine H1 receptor antagonist with anti-allergic and moderate anticholinergic activity [1,3,4] Its core mechanism includes competitive H1R antagonism (blocking histamine-mediated allergic reactions) and moderate muscarinic receptor (M1-M3) blocking [1] Indications include allergic rhinitis, chronic urticaria and allergic conjunctivitis, to relieve symptoms such as sneezing, runny nose, itching and urticaria-like skin lesions [3,4] Moderate blood-brain barrier penetration leads to sedative side effects, a typical feature of first-generation antihistamines [3] The long elimination half-life (10-12 hours) supports twice-daily dosing (1 mg each time) in adults. [3] It has comparable anti-allergic efficacy to other first-generation antihistamines, but its muscarinic side effects are slightly higher [1,4] |
| Molecular Formula |
C28H30N2O8
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| Molecular Weight |
522.55
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| Exact Mass |
522.2
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| Elemental Analysis |
C, 64.36; H, 5.79; N, 5.36; O, 24.49
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| CAS # |
3978-86-7
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| Related CAS # |
Azatadine; 3964-81-6
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| PubChem CID |
5281066
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| Appearance |
White to off-white solid powder
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| Boiling Point |
450.1ºC at 760 mmHg
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| Melting Point |
152-154°
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| Flash Point |
226ºC
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| LogP |
3.069
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
38
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| Complexity |
536
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O([H])C(/C(/[H])=C(/[H])\C(=O)O[H])=O.O([H])C(/C(/[H])=C(/[H])\C(=O)O[H])=O.N1(C([H])([H])[H])C([H])([H])C([H])([H])/C(=C2/C3=C(C([H])=C([H])C([H])=N3)C([H])([H])C([H])([H])C3=C([H])C([H])=C([H])C([H])=C/23)/C([H])([H])C1([H])[H]
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| InChi Key |
SGHXFFAHXTZRQM-SPIKMXEPSA-N
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| InChi Code |
InChI=1S/C20H22N2.2C4H4O4/c1-22-13-10-16(11-14-22)19-18-7-3-2-5-15(18)8-9-17-6-4-12-21-20(17)19;2*5-3(6)1-2-4(7)8/h2-7,12H,8-11,13-14H2,1H3;2*1-2H,(H,5,6)(H,7,8)/b;2*2-1-
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| Chemical Name |
(Z)-but-2-enedioic acid;2-(1-methylpiperidin-4-ylidene)-4-azatricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,11,13-hexaene
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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 (4.78 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 (4.78 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 (4.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (191.37 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9137 mL | 9.5685 mL | 19.1369 mL | |
| 5 mM | 0.3827 mL | 1.9137 mL | 3.8274 mL | |
| 10 mM | 0.1914 mL | 0.9568 mL | 1.9137 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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