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.

Physicochemical Properties

Molecular Formula	C28H30N2O8
Molecular Weight	522.55
Exact Mass	522.2
Elemental Analysis	C, 64.36; H, 5.79; N, 5.36; O, 24.49
CAS #	3978-86-7
Related CAS #	Azatadine; 3964-81-6
PubChem CID	5281066
Appearance	White to off-white solid powder
Boiling Point	450.1ºC at 760 mmHg
Melting Point	152-154°
Flash Point	226ºC
LogP	3.069
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	4
Heavy Atom Count	38
Complexity	536
Defined Atom Stereocenter Count	0
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]
InChi Key	SGHXFFAHXTZRQM-SPIKMXEPSA-N
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-
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
Synonyms	SCH 10649; azatadine maleate; SCH10649; SCH-10649; Idulamine; Idulian; Lergocil; Optimine; Zadine
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

Targets	Histamine receptor ( IC50 = 6.5 nM ); Cholinergic ( IC50 = 10 nM )
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]
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]
Animal Protocol	0.01 mg/kg, 0.739 mg/kg and 0.86 mg/kg guinea-pig
References	[1]. Agents Actions . 1974 Oct;4(4):264-70. [2]. Appl Environ Microbiol . 1996 Sep;62(9):3477-9. [3]. Clin Pharmacokinet . 1991 Nov;21(5):372-93. [4]. Asian Pac J Allergy Immunol . 1990 Dec;8(2):103-7.
Additional Infomation	Azatadine maleate is the dimaleate salt of azatadine. It has a role as a H1-receptor antagonist and an anti-allergic agent. It contains an azatadine. See also: Azatadine maleate; pseudoephedrine sulfate (component of).

Solubility Data

Solubility (In Vitro)

DMSO: ~105 mg/mL (~200.9 mM) Water: ~105 mg/mL (~200.9 mM) Ethanol: <1 mg/mL

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. 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. 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. 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.  (Please use freshly prepared in vivo formulations for optimal results.)

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.