MCF-7 cells' ability to grow is inhibited by buclizine (0.1–100 μM; 72 hours) [2]. In a dose-dependent manner, buclizine (9.625-77 μM; 72 hours) stops the cell cycle in the G1 phase [2]. In MCF-7 cells, buclizine (0-75 μM; 72 hours) boosts pro-apoptotic MCL-1S expression while decreasing the expression of cell cycle regulatory proteins and TCTP (translationally controlled tumor protein) [2].

Rats are strongly teratogenic to buclizine diHClide (30-200 mg/kg; gestation days 10 to 15 and 12 to 15) [3].

Cell Proliferation Assay[2]
Cell Types: MCF-7 Cell
Tested Concentrations: 0-100 μM
Incubation Duration: 72 hrs (hours)
Experimental Results: demonstrated considerable growth inhibition (IC50=19.18 μM).

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Cell cycle analysis[2]
Cell Types: MCF-7 Cell
Tested Concentrations: 9.625, 19.25, 38.5 and 77 μM
Incubation Duration: 72 hrs (hours)
Experimental Results: The percentage of cells in G1 phase increased to 73% at 77 μM.

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Western Blot Analysis[2]
Cell Types: MCF-7 Cell
Tested Concentrations: 0-75 μM
Incubation Duration: 72 hrs (hours)
Experimental Results: TCTP expression diminished by 40% at 75 μM. The expression of cyclin D1, cyclin D3, CDK2 and CDK4 diminished after 72 hrs (hours).

Animal/Disease Models: 87 adult female rats, weighing 240±20 grams [3]
Doses: 30, 40, 60, 100, 200 mg/kg
Doses: 30-200 mg/kg; pregnancy days 10 to 15 and Results on days 12 to 15: Dose levels of 60-100 mg/kg resulted in malformations in 100% of the pups.

Absorption, Distribution and Excretion
Rapidly absorbed after oral administration. Metabolism/Metabolites Hepatic.

[1]. Buclizine. Profiles Drug Subst Excip Relat Methodol. 2011;36:1-33.

[2]. Interaction of antihistaminic drugs with human translationally controlled tumor protein (TCTP) as novel approach for differentiation therapy. Oncotarget. 2016 Mar 29;7(13):16818-39.

[3]. Teratogenic effect of buclizine and hydroxyzine in the rat and chlorcyclizine in the mouse. Am J Obstet Gynecol. 1966 May 1;95(1):109-11.

Buclizine is an N-alkylpiperazine drug containing (4-chlorophenyl)(phenyl)methyl and 4-tert-butylbenzyl groups. It has antiemetic, cholinergic, histamine antagonistic, local anesthetic, and central nervous system depressant effects. It is an N-alkylpiperazine drug belonging to the monochlorobenzene class of compounds. It is the conjugate base of Buclizine (2+). Buclizine is an antihistamine with antiemetic and anticholinergic effects, belonging to the piperazine derivative class of drugs. It is manufactured by Stuart Pharms and was first approved by the U.S. Food and Drug Administration (FDA) in 1957. Subsequently, there were rumors that its syrup formulation could effectively stimulate appetite in children, but this indication has not been confirmed. In addition to the above indications, Buclizine is also used to treat migraine attacks and nausea and vomiting during pregnancy. Buclizine is a piperazine histamine H1 receptor antagonist, primarily with antiemetic and antivertigo effects. Buccrizine binds to and blocks the activity of histamine H1 receptors, thereby preventing symptoms caused by histamine activity. Buccrizine exerts its antiemetic effect by binding to and blocking muscarinic and histamine receptors in the vomiting center of the central nervous system. This may help inhibit activation of the chemoreceptor trigger zone (CTZ), thus alleviating nausea and vomiting. Pharmacological Indications: For the prevention and treatment of nausea, vomiting, and dizziness caused by motion sickness and vertigo (vertigo caused by other diseases). Mechanism of Action: Vomiting is essentially a protective mechanism to clear irritants or other harmful substances from the upper digestive tract. Vomiting is controlled by the vomiting center in the medulla oblongata of the brain, of which the chemoreceptor trigger zone (CTZ) is an important component. The vomiting center contains abundant muscarinic cholinergic neurons and histaminergic neurons. These types of neurons are particularly involved in signal transmission from the vestibular organs to the vomiting center. Motion sickness mainly involves various sensory stimuli leading to overexcitation of these pathways. Therefore, the mechanism of action of bukelizine is to block histamine receptors in the vomiting center, thereby reducing the activity of these pathways. Furthermore, due to its anticholinergic properties, muscarinic receptors are also blocked.

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Pharmacodynamics
Bukelizine is a piperazine antihistamine used as an anti-vertigo/antiemetic. It is used to prevent and treat nausea, vomiting, and dizziness associated with motion sickness. It is also used to treat vertigo caused by diseases affecting the vestibular system. While the mechanisms by which bukelizine exerts its antiemetic and anti-vertigo effects are not fully elucidated, its central anticholinergic properties are partly responsible. The drug inhibits labyrinthine excitability and vestibular stimulation and may affect the medullary chemoreceptor trigger zone. It also has anticholinergic, antihistamine, central nervous system depressant, and local anesthetic effects.

C28H33N2CL

433.02802

432.233

82-95-1

Buclizine dihydrochloride;129-74-8

6729

Typically exists as solid at room temperature

6.42

0

2

6

31

514

0

ClC1C=CC(C(N2CCN(CC3C=CC(C(C)(C)C)=CC=3)CC2)C2C=CC=CC=2)=CC=1

MOYGZHXDRJNJEP-UHFFFAOYSA-N

InChI=1S/C28H33ClN2/c1-28(2,3)25-13-9-22(10-14-25)21-30-17-19-31(20-18-30)27(23-7-5-4-6-8-23)24-11-15-26(29)16-12-24/h4-16,27H,17-21H2,1-3H3

1-[(4-tert-butylphenyl)methyl]-4-[(4-chlorophenyl)-phenylmethyl]piperazine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

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.

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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).

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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)

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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).

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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

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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.

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