| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| 500mg |
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Purity: ≥98%
Buclizine hydrochloride (AH-2526, UCB 4445; AH2526;UCB-4445, Buclina, Longifene, Posdel, Vibazine), the hydrochloride salt of buclizine which is used for motion sickness, is a piperazine derivative and a sedating antihistamine with antimuscarinic and moderate sedative action. Buclizine has been used to treat and prevent motion sickness-related nausea, vomiting, and dizziness. It has also been used to treat vertigo in conditions affecting the vestibular apparatus.
| Targets |
Histamine receptor; Cholinergic
Histamine H1 receptor (H1R) (human H1R, Ki=0.8 nM; rat H1R, Ki=1.2 nM) [1] Translationally Controlled Tumor Protein (TCTP) (human TCTP, Ki=12.3 μM) [3] |
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| ln Vitro |
In vitro activity: Buclizine hydrochloride, a piperazine derivative, is a moderately sedative antihistamine that has an antimuscarinic and sedative effect. Motion sickness-related nausea, vomiting, and dizziness can be prevented and treated with buclizine. Furthermore, in conditions impacting the vestibular apparatus, it has been utilized to treat vertigo. While the exact mechanism underlying buclizine's antiemetic and antivertigo effects is yet unknown, its central anticholinergic properties play a role. The medication may have an impact on the medullary chemoreceptor trigger zone and decreases vestibular stimulation and labyrinth excitability. Its other properties include central nervous system depression, anticholinergic, antihistaminic, and local anesthetic effects.[1]
Human peripheral blood basophils stimulated with anti-IgE (1 μg/mL) were treated with Buclizine HCl (UCB-4445) (0.1 μM-10 μM). It dose-dependently inhibited histamine release, with maximum inhibition of 70% at 10 μM and IC50=1.5 μM [1] - Isolated guinea pig tracheal smooth muscle strips pre-contracted with histamine (1 μM) were treated with Buclizine HCl (UCB-4445) (0.1 μM-10 μM). It induced concentration-dependent relaxation, EC50=1.8 μM, confirming H1R antagonistic activity [1] - Human leukemia HL-60 cells and melanoma A375 cells were treated with Buclizine HCl (UCB-4445) (10 μM-50 μM) for 72 hours. At 30 μM, it induced HL-60 cell differentiation (CD11b expression increased by 2.8-fold) and inhibited A375 cell proliferation by 45% (MTT assay). Western blot showed upregulated p53 and p21 expression, downregulated TCTP expression [3] - Fluorescence polarization assay confirmed Buclizine HCl (UCB-4445) specifically bound to human TCTP, with Ki=12.3 μM, disrupting TCTP-p53 interaction [3] |
| ln Vivo |
Passive cutaneous anaphylaxis (PCA) model in rats: Oral administration of Buclizine HCl (UCB-4445) (5 mg/kg, 10 mg/kg) 1 hour before antigen challenge dose-dependently inhibited skin wheal formation, with 75% inhibition at 10 mg/kg [1]
- Motion sickness model in mice: Intraperitoneal injection of Buclizine HCl (UCB-4445) (20 mg/kg) 30 minutes before rotational stimulation reduced emetic-like behaviors (retching, freezing) by 68% compared to vehicle [1] - Teratogenicity study in rats: Pregnant rats were given Buclizine HCl (UCB-4445) (50 mg/kg/day, oral) from gestation days 6 to 15. Fetal examination showed 18% incidence of skeletal malformations (rib hypoplasia) and 12% incidence of visceral anomalies (renal hypoplasia) [2] |
| Enzyme Assay |
H1R binding assay: Prepare membrane fractions from HEK293 cells expressing human H1R or rat brain tissue. Incubate membranes with [3H]-pyrilamine (0.5 nM) and various concentrations of Buclizine HCl (UCB-4445) (0.01 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]
- TCTP binding assay: Recombinant human TCTP was incubated with fluorescently labeled p53 peptide and different concentrations of Buclizine HCl (UCB-4445) (1 μM-100 μM) at 37°C for 90 minutes. Measure fluorescence polarization values to assess binding affinity and calculate Ki [3] |
| Cell Assay |
Basophil histamine release assay: Isolate human peripheral blood basophils via density gradient centrifugation. Resuspend cells in buffer and pre-treat with Buclizine HCl (UCB-4445) (0.1 μM-10 μM) for 30 minutes. Stimulate with anti-IgE (1 μg/mL) for 60 minutes at 37°C. Centrifuge to collect supernatant and measure histamine concentration via fluorometric assay [1]
- Tumor cell differentiation and proliferation assay: Seed HL-60/A375 cells in 6-well plates (5×105 cells/well) and incubate for 24 hours. Treat with Buclizine HCl (UCB-4445) (10 μM-50 μM) for 72 hours. Detect HL-60 cell differentiation via flow cytometry (CD11b marker); assess A375 cell viability via MTT assay. Extract total protein to detect TCTP, p53, and p21 expression via Western blot [3] - Tracheal smooth muscle relaxation assay: Isolate guinea pig tracheal strips, 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 Buclizine HCl (UCB-4445) (0.1 μM-10 μM) cumulatively and record tension changes [1] |
| Animal Protocol |
PCA rat model: Male Wistar rats (150-200 g) were intradermally injected with anti-ovalbumin IgE (0.1 mL) on the back. After 48 hours, Buclizine HCl (UCB-4445) was dissolved in 0.5% carboxymethylcellulose sodium and administered via oral gavage (5 mg/kg, 10 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]
- Mouse motion sickness model: Male ICR mice (18-22 g) were randomly divided into vehicle and Buclizine HCl (UCB-4445) (20 mg/kg) groups. The drug was dissolved in physiological saline and administered via intraperitoneal injection 30 minutes before rotational stimulation (10 rpm for 30 minutes). Record emetic-like behaviors during and 1 hour post-stimulation [1] - Rat teratogenicity study: Female Sprague-Dawley rats were mated, and gestation was confirmed by vaginal plug. From gestation days 6 to 15, Buclizine HCl (UCB-4445) (50 mg/kg/day) was administered via oral gavage. On gestation day 20, rats were euthanized, and fetuses were removed for skeletal staining (Alizarin red-Alcian blue) and visceral dissection to detect abnormalities [2] |
| ADME/Pharmacokinetics |
Absorption: The oral bioavailability in the human body is 65-70%; the peak plasma concentration (Cmax) is reached 2-3 hours after oral administration (50 mg dose: Cmax = 220 ng/mL) [1]
- Distribution: The volume of distribution (Vd) in the human body is 3.2 L/kg; the brain/plasma concentration ratio is 0.4, indicating that it has moderate blood-brain barrier penetration [1] - Metabolism: It is mainly metabolized in the liver by cytochrome P450 (CYP) 2D6 and 3A4 into inactive metabolites [1] - Excretion: 55% of the dose is excreted in feces (40% as metabolites, 15% as the original drug), and 40% is excreted in urine (mainly as metabolites). The elimination half-life (t1/2) in the human body is 14-16 hours [1] - Plasma protein binding rate: The plasma protein binding rate of buclazine hydrochloride (UCB-4445) in human plasma is 85-90% [1] |
| Toxicity/Toxicokinetics |
Acute toxicity: LD50 in rats and mice >1000 mg/kg (oral); no deaths or serious clinical symptoms (convulsions, respiratory depression) were reported [1] - Chronic toxicity: No significant hepatotoxicity or hematologic abnormalities were observed in rats after 6 months of oral administration of buclazine hydrochloride (UCB-4445) (50 mg/kg/day) [1] - Teratogenicity: High doses (50 mg/kg/day) in pregnant rats were teratogenic, causing skeletal and visceral malformations in the fetus [2] - Clinical side effects: Sedation (25-30% of patients), dry mouth (15-20%) and dizziness (10-15%) were caused due to moderate blood-brain barrier penetration. No significant cardiotoxicity [1] - Drug interactions: Co-administration with CYP3A4 inhibitors (e.g., ketoconazole) can increase plasma concentrations of bukelizine by 40%; enhance the sedative effects of alcohol and benzodiazepines [1]
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| References | |
| Additional Infomation |
Buccridine hydrochloride is the hydrochloride salt of buccridine prepared by reacting it with 2 equivalents of hydrogen chloride. It has the effects of central nervous system depressant, local anesthetic, histamine antagonist, cholinergic antagonist, and antiemetic. It contains the buccridine (2+) ion. Buccridine hydrochloride is the hydrochloride form of buccridine, a piperazine histamine H1 receptor antagonist primarily with antiemetic and antivertigo effects. Buccridine binds to and blocks the activity of histamine H1 receptors, thereby preventing histamine-induced symptoms. Buccridine exerts its antiemetic effect by binding to and blocking muscarinic and histamine receptors in the vomiting center of the central nervous system. This may prevent activation of the chemoreceptor trigger zone (CTZ) and may alleviate nausea and vomiting. Buccridine hydrochloride (UCB-4445) is a first-generation histamine H1 receptor antagonist with anti-allergic, anti-motion sickness, and potential antitumor activities [1,3].
Its core mechanisms include competitive H1R antagonism (blocking histamine-mediated allergic reactions) and binding to TCTP (disrupting TCTP-p53 interaction to induce tumor cell differentiation) [1,3]. Indications include prevention and treatment of motion sickness (nausea, vomiting, vertigo) and allergic rhinitis/urticaria (relieving sneezing, itching) [1]. Moderate blood-brain barrier penetration results in sedative side effects, which distinguishes it from second-generation H1 receptor antagonists that do not have sedative effects. [1] High doses are teratogenic in rats, suggesting caution during pregnancy. [2] Long elimination half-life (14-16 hours) supports once-daily dosing in adults. [1] |
| Molecular Formula |
C28H35CL3N2
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| Molecular Weight |
505.95
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| Exact Mass |
504.186
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| Elemental Analysis |
C, 66.47; H, 6.97; Cl, 21.02; N, 5.54
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| CAS # |
129-74-8
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| Related CAS # |
Buclizine; 82-95-1
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| PubChem CID |
65463
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| Appearance |
White to off-white solid powder
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| Boiling Point |
520.1ºC at 760 mmHg
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| Melting Point |
230-240ºC
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| Flash Point |
268.3ºC
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| Vapour Pressure |
6.44E-11mmHg at 25°C
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| LogP |
8.024
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
33
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| Complexity |
514
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC(C)(C)C1=CC=C(C=C1)CN2CCN(CC2)C(C3=CC=CC=C3)C4=CC=C(C=C4)Cl.Cl.Cl
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| InChi Key |
SDBHDSZKNVDKNU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H33ClN2.2ClH/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;2*1H
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| Chemical Name |
1-[(4-tert-butylphenyl)methyl]-4-[(4-chlorophenyl)-phenylmethyl]piperazine;dihydrochloride
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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) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9765 mL | 9.8824 mL | 19.7648 mL | |
| 5 mM | 0.3953 mL | 1.9765 mL | 3.9530 mL | |
| 10 mM | 0.1976 mL | 0.9882 mL | 1.9765 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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