| Size | Price | Stock | Qty |
|---|---|---|---|
| 250mg |
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| 500mg |
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| 1g | |||
| Other Sizes |
| Targets |
Pizotifen malate primarily targets serotonin (5-HT) receptors, specifically the 5-HT2A and 5-HT2C subtypes. It exhibits exceptionally high affinity for the human recombinant 5-HT2A receptor with a Ki value of approximately 2.0 nM, and affinity for the 5-HT2C receptor with a Ki value of approximately 8.4 nM. Additionally, it has high affinity for the 5-HT1C binding site, displays potent antagonistic activity at histamine H1 receptors (Ki ~1.9 nM), and has weak antimuscarinic effects.
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| ln Vitro |
Pizotifen malate (BC-105 malate) is a strong antagonist of the 5-HT2 receptor that has a high affinity for the binding region of the 5-HT1C [1]. Pizotifen is an anti-5-HT2A receptor antagonist that prevents platelet aggregation generated by ADP that is increased by serotonin [2].
Pizotifen significantly inhibits the proliferation, migration, and invasion of human HCT116 colorectal cancer cells. As a 5-HT2A receptor antagonist, it inhibits serotonin-enhanced ADP-induced platelet aggregation in both human and murine platelet preparations. In the central nervous system, preliminary studies suggest that pizotifen may activate the ERK signaling pathway and provide neuroprotective effects, transiently activating ERK and inhibiting its overactivation in striatal cells such as Hdh(Q111/Q111) cells. |
| ln Vivo |
Fetal weight was considerably lowered by all doses of pethidine and benzofen malate (BC-105 malate); placental weight was only significantly reduced at the intermediate level and only after 0.6 and 1.2 mg/kg of pethidine. It didn't drastically drop until after bentifen malate. There was no difference observed between the treated and control groups in terms of implantation, viable pregnancies, stillbirths, resorptions, and external, skeletal, and visceral abnormalities. There was no discernible difference between the treatment group's and the negative control group's number of chromosomal abnormalities in the mice's bone marrow cells. Testing for micronuclei revealed no rise in micronucleus frequency as compared to controls. Following two increased dosages of benzofen maleate and pipethiazide, the mitotic index was comparatively lower in the experimental group [3].
In mice, oral administration of pizotifen at 3 mg/kg for 5 days almost completely inhibits serotonin-enhanced ADP-induced platelet aggregation. In the R6/2 Huntington's disease mouse model, pizotifen activates the ERK signaling pathway in the striatum, mitigates neurodegeneration, and enhances motor performance. In anesthetized monkeys, pizotifen blocks vascular responses to histamine, while attenuating internal carotid responses to 5-HT and potentiating external carotid 5-HT responses. Furthermore, in conscious dogs, pizotifen exhibited considerable agonist activity upon both local and systemic administration, suggesting that its clinical efficacy in migraine prophylaxis derives at least in part from an as-yet-unelucidated agonist mechanism. |
| Enzyme Assay |
The receptor binding affinity of Pizotifen malate is typically assessed using a cell-free radioligand binding assay. The procedure generally involves incubating membrane homogenates prepared from specific human or animal brain tissues (or human recombinant systems) with a fixed concentration of a high-affinity, radiolabeled ligand in a binding buffer, in the presence of a range of competing concentrations of Pizotifen malate (typically from 10^-10 to 10^-4 M). After incubation for a set period (e.g., 60-90 minutes at room temperature or 37°C), bound and unbound radioligands are separated via rapid vacuum filtration over glass fiber filters, followed by washing. Residual radioactivity on the filters is then quantified using a liquid scintillation counter to generate competitive inhibition curves. The IC50 is determined via nonlinear regression, which is subsequently converted to a Ki value using the Cheng-Prusoff equation. For example, for a specific receptor, this non-cell filtration method yields a Ki value of 2.0 nM for Pizotifen malate at the 5-HT2A receptor.
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| Cell Assay |
To evaluate the cellular effects of Pizotifen malate, cell lines such as human HCT116 or MCF-7 are typically used. A standard procedure involves culturing cells in complete medium (e.g., RPMI 1640 or DMEM supplemented with 10% fetal bovine serum and 1% antibiotics) at 37°C in a 5% CO?? incubator. Once the cells reach the logarithmic growth phase, they are seeded into 96-well plates at an appropriate density (e.g., 7,500 cells/well) and allowed to attach overnight. The next day, the old medium is replaced with a working medium containing gradient concentrations of pizotifen (e.g., 10 µM, 5 µM, etc.), accompanied by a vehicle control group, with each treatment typically having 3-6 replicate wells. After a specific treatment period (e.g., 5 hours or 72 hours), cell viability is assessed using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay or the CCK-8 method. Alternatively, cell migration and invasion are analyzed using Transwell chamber assays. At the end of the experiment, the optical density of each well is measured with a microplate reader to calculate the relative inhibition rate or activity percentage.
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| Animal Protocol |
Using a mouse teratological and cytogenetical evaluation study as an example, Swiss mice are used as the animal model. Pizotifen malate is administered orally via gavage at doses of 0.24, 0.6, and 1.2 mg/kg from day 4 to day 16 of gestation. The control group is treated with distilled water. On gestation day 19, the mice are sacrificed for cytogenetic examination and uterine content analysis, which includes determining the number of implantations, live fetuses, abnormal fetuses, dead fetuses, and resorptions. Furthermore, all live fetuses are inspected for external, visceral, and skeletal malformations, while bone marrow cells are collected for chromosome aberration analysis and a micronucleus test.
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| ADME/Pharmacokinetics |
Following oral administration, pizotifen is absorbed rapidly and almost completely from the gastrointestinal tract, with an absolute bioavailability of approximately 78%. Peak plasma concentrations are reached at about 5 hours post-dose. The drug exhibits very high plasma protein binding, at approximately 91%. Pizotifen undergoes extensive metabolic processing in the liver, primarily via glucuronidation, producing the main metabolite, the N-glucuronide conjugate, which accounts for at least 50% of the plasma exposure. For elimination, approximately 55% of the administered dose is excreted as metabolites in the urine, 18% in the feces, and less than 1% is excreted renally as unchanged drug. The terminal elimination half-life of both pizotifen and its N-glucuronide metabolite is approximately 23 hours.
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| Toxicity/Toxicokinetics |
In clinical use, the most common side effects of pizotifen are drowsiness (usually seen within the first 1-2 weeks of treatment, which may diminish with continued use), increased appetite, and weight gain. Animal toxicology studies indicate that at higher doses, pizotifen can reduce the mitotic index in bone marrow cells, suggesting potential for mild embryotoxicity and teratogenic potential (though fetal malformation rates do not differ significantly from controls). Results from mouse bone marrow micronucleus tests and chromosome aberration analyses show no significant elevation in the frequency of micronuclei or chromosomal abnormalities, suggesting a low genotoxic risk. Other possible adverse reactions include dizziness, dry mouth, nausea, and, rarely, hepatotoxicity and seizures. It is important to note that the drug has CNS depressant effects; patients should avoid driving and operating heavy machinery during treatment.
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| References |
[1]. Mylecharane EJ, et al. 5-HT2 receptor antagonists and migraine therapy. J Neurol. 1991;238 Suppl 1:S45-52.
[2]. Lin OA, et al. The antidepressant 5-HT2A receptor antagonists pizotifen and cyproheptadine inhibit serotonin-enhanced platelet function. PLoS One. 2014 Jan 23;9(1):e87026. [3]. Ujházy E, et al. Teratological and cytogenetical evaluation of two antihistamines (pipethiadene and pizotifen maleate) in mice. Agents Actions. 1988 Apr;23(3-4):376-8 |
| Additional Infomation |
Pizotifen malate is an malate formed by the reaction of equimolar amounts of Pizotifen with malic acid. It is a sedative antihistamine with potent serotonin antagonism and weak antimuscarinic activity, used to treat migraines and prevent cluster headache attacks. It simultaneously acts as a histamine antagonist, muscarinic antagonist, and serotonin antagonist. Its molecular structure contains Pizotifen (1+).
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| Molecular Formula |
C23H27NO5S
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| Molecular Weight |
429.5292
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| Exact Mass |
429.16
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| CAS # |
5189-11-7
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| Related CAS # |
Pizotifen;15574-96-6
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| PubChem CID |
168993
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| Appearance |
Typically exists as solid at room temperature
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| Boiling Point |
436.7ºC at 760 mmHg
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| Melting Point |
185-186° (dec)
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| Flash Point |
217.9ºC
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| LogP |
4.023
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
30
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| Complexity |
535
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C([H])=C([H])C2=C1C([H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1/C/2=C1\C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C\1([H])[H].O([H])C([H])(C(=O)O[H])C([H])([H])C(=O)O[H]
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| InChi Key |
IWAWCPZVTXCFKD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H21NS.C4H6O5/c1-20-11-8-15(9-12-20)19-16-5-3-2-4-14(16)6-7-18-17(19)10-13-21-18;5-2(4(8)9)1-3(6)7/h2-5,10,13H,6-9,11-12H2,1H3;2,5H,1H2,(H,6,7)(H,8,9)
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| Chemical Name |
2-hydroxybutanedioic acid;1-methyl-4-(6-thiatricyclo[8.4.0.03,7]tetradeca-1(14),3(7),4,10,12-pentaen-2-ylidene)piperidine
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
DMSO : ~50 mg/mL (~116.41 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.82 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 (5.82 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3281 mL | 11.6406 mL | 23.2813 mL | |
| 5 mM | 0.4656 mL | 2.3281 mL | 4.6563 mL | |
| 10 mM | 0.2328 mL | 1.1641 mL | 2.3281 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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