Cyclizine 2HCl (Marezine; Ciclizina; Nautazine; Valoid; Neo-devomit), the dihydrochloride salt of cyclizine, is a potent and 1st generation histamine H1 receptor antagonist of the piperazine class with anticholinergic and antiemetic properties. It has been used as a medication to treat and prevent vertigo, motion sickness, nausea, and vomiting. The exact mechanism through which cyclizine prevents vomiting and vertigo is still unknown. Cyclizine decreases the sensitivity of the labyrinthine apparatus and raises the tone of the lower oesophageal sphincter. It might suppress the area of the midbrain referred to as the emetic center.

Physicochemical Properties

Molecular Formula	C18H24CL2N2
Molecular Weight	339.3
Exact Mass	302.155
Elemental Analysis	C, 63.72; H, 7.13; Cl, 20.90; N, 8.26
CAS #	5897-18-7
Related CAS #	Cyclizine; 82-92-8; Cyclizine lactate; 5897-19-8; Cyclizine hydrochloride; 303-25-3
PubChem CID	67533
Appearance	Solid powder
LogP	3.701
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	3
Heavy Atom Count	22
Complexity	253
Defined Atom Stereocenter Count	0
SMILES	CN1CCN(CC1)C(C2=CC=CC=C2)C3=CC=CC=C3.Cl.Cl
InChi Key	CKLJCUGYMOMAEJ-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H22N2.2ClH/c1-19-12-14-20(15-13-19)18(16-8-4-2-5-9-16)17-10-6-3-7-11-17;;/h2-11,18H,12-15H2,1H3;2*1H
Chemical Name	1-benzhydryl-4-methylpiperazine;dihydrochloride
Synonyms	Cyclizine2HCl; Marezine; Ciclizina; Nautazine; Valoid; Neo-devomit
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	Histamine H1 receptor
ln Vitro	In vitro activity: Cyclizine belongs to the piperazine class of drugs that block histamine H1 receptors. It has antiemetic and anticholinergic qualities. The exact mechanism through which cyclizine prevents vomiting and vertigo is still unknown. Cyclizine decreases the sensitivity of the labyrinthine apparatus and raises the tone of the lower oesophageal sphincter. It might suppress the area of the midbrain referred to as the emetic center.
ln Vivo	Cyclizine is converted to norcyclizine, its N-demethylated derivative, which has less antihistaminic (H1) action than cycliziine. When taken orally, the effects start to manifest in 30 minutes, reach their peak in 1–2 hours, and, in the case of cyclizine, last for 4–6 hours. A single oral dose of 50 mg of cyclizine administered to healthy adult volunteers produced a peak plasma concentration of about 70 ng/mL about two hours after the drug was administered. The half-life of plasma elimination is roughly 20 hours.
Animal Protocol	Naive male CDI mice (Charles River) weighing 25-30 g 1, 10 mg/kg s.c.; locomotor activity (crossings) measured every 15 min for 2 hr.
References	[1]. The effects of H1-antihistamines on the nitric oxide production by RAW 264.7 cells with respect to their lipophilicity. Int Immunopharmacol. 2009 Jul;9(7-8):990-5. [2]. Inhibition of histamine release from human lung in vitro by antihistamines and related drugs. Br J Pharmacol. 1980 Aug;69(4):663-7. [3]. Effects of antihistaminics on locomotor activity in mice. Comparison with opiate and amphetamine-induced hyperactivity. Gen Pharmacol. 1991;22(2):293-6.

Solubility Data

Solubility (In Vitro)

DMSO: ~7 mg/mL (~20.6 mM) Water: ~68 mg/mL (~200.4 mM) Ethanol: <1 mg/mL

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	2.9472 mL	14.7362 mL	29.4724 mL
	5 mM	0.5894 mL	2.9472 mL	5.8945 mL
	10 mM	0.2947 mL	1.4736 mL	2.9472 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.