Meclizine (Meclozine) di-HCl monohydrate is an antihistamine that reversibly inhibits the interaction of histamine with H1 receptors. Meclizine di-HCl monohydrate is a piperazine H1 antagonist and an effective anti-motion sickness agent. Meclizine di-HCl monohydrate crosses the BBB (blood-brain barrier). Meclizine di-HCl monohydrate is a constitutive androstane receptor (CAR) agonist in mice and an inverse agonist of human CAR. Meclizine di-HCl monohydrate may be used in research into polyglutamine toxicity disorders such as Huntington's disease.

Physicochemical Properties

Molecular Formula	C25H31CL3N2O
Molecular Weight	481.89
Exact Mass	462.139
CAS #	31884-77-2
Related CAS #	Meclizine-d8 dihydrochloride;1432062-16-2;Meclizine;569-65-3
PubChem CID	173612
Appearance	Typically exists as solid at room temperature
Melting Point	210-213℃
LogP	6.971
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	5
Heavy Atom Count	31
Complexity	448
Defined Atom Stereocenter Count	0
SMILES	CC1=CC(=CC=C1)CN2CCN(CC2)C(C3=CC=CC=C3)C4=CC=C(C=C4)Cl.Cl.Cl.O
InChi Key	KDLHYOMCWBWLMM-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H27ClN2.2ClH.H2O/c1-20-6-5-7-21(18-20)19-27-14-16-28(17-15-27)25(22-8-3-2-4-9-22)23-10-12-24(26)13-11-23;;;/h2-13,18,25H,14-17,19H2,1H3;2*1H;1H2
Chemical Name	1-[(4-chlorophenyl)-phenylmethyl]-4-[(3-methylphenyl)methyl]piperazine;hydrate;dihydrochloride
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
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	H1 Receptor
ln Vitro	Meclizine (Meclozine; 50 µM; 24 hours) dihydrochloride monohydrate notably boosts cell survival in STHdhQ111/111 cells 24 hours following serum withdrawal, presumably via inhibiting apoptosis as determined by caspase 3 and 7 breakage. With a maximal efficacy of 218% enhanced survival over vehicle, the rescue is dose-dependent, with an EC50 of 17.3 µm. Meclizine dihydrochloride monohydrate inhibits the death of mutant (STHdhQ111/111) and wild-type (STHdhQ7/7) striatal cells produced by serum withdrawal in cells expressing polyglutamine (polyQ)-expanded huntingtin[2].
ln Vivo	Mice protected against renal ischemia by meclizine (Meclozine; 10-100 mg/kg; ip) dihydrochloride monohydrate. In mice, kidney protection is demonstrated by pretreatment with 100 mg/kg of meclizine 17 or 24 hours before ischemia. Meclizine dihydrochloride monohydrate increases glycolysis and directly inhibits the Kennedy route of phosphatidylethanolamine production, hence lowering mitochondrial oxygen consumption[4].
Cell Assay	Cell Viability Assay[2] Cell Types: The murine striatal cells expressing wild-type (STHdhQ7/7) or mutant (STHdhQ111/111) huntingtin protein Tested Concentrations: 50 µM Incubation Duration: 24 hrs (hours) Experimental Results: Dramatically increased cell survival in STHdhQ111/111 cells at 24 h after the removal of serum. Western Blot Analysis[2] Cell Types: Mutant (STHdhQ111/111) and wild-type (STHdhQ7/7) striatal cells Tested Concentrations: 50 µM Incubation Duration: 0, 4, 10, 24 hrs (hours) Experimental Results: Suppressed apoptosis, based on caspase 3 and 7 cleavage.
Animal Protocol	Animal/Disease Models: 8-10 wk old male C57BL/6 mice[4] Doses: 10, 30, 60 or 100 mg/kg Route of Administration: Administered intraperitoneally (ip) Experimental Results: Protected mice from kidney ischemia-reperfusion injury.
References	[1]. Safety and Efficacy in the Treatment and Prevention of Motion Sickness. [2]. Meclizine is neuroprotective in models of Huntington's disease. Hum Mol Genet. 2011 Jan 15;20(2):294-300. [3]. Meclizine Is an Agonist Ligand for Mouse Constitutive Androstane Receptor (CAR) and an Inverse Agonist for Human CAR. [4]. Meclizine Preconditioning Protects the Kidney Against Ischemia-Reperfusion Injury. EBioMedicine. 2015 Jul 29;2(9):1090-101.
Additional Infomation	Meclizine hydrochloride is a diarylmethane. Meclizine Hydrochloride is the hydrochloride salt form of meclizine, a synthetic piperazine with anti-emetic, sedative and histamine H1 antagonistic properties. Meclizine hydrochloride blocks the H1 histamine receptor and prevents the symptoms that are caused by histamine activity on capillaries, bronchial and gastrointestinal smooth muscles, including vasodilation, increased capillary permeability, bronchoconstriction, and spasmodic contraction of gastrointestinal smooth muscles. Meclizine hydrochloride may exert its antiemetic effects by its anticholinergic actions or due to a direct effect on the medullary chemoreceptive trigger zone. A histamine H1 antagonist used in the treatment of motion sickness, vertigo, and nausea during pregnancy and radiation sickness. See also: Meclizine (has active moiety) ... View More ...

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0752 mL	10.3758 mL	20.7516 mL
	5 mM	0.4150 mL	2.0752 mL	4.1503 mL
	10 mM	0.2075 mL	1.0376 mL	2.0752 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.