| Size | Price | Stock | Qty |
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| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
The primary pharmacological target of piperazine is the neuromuscular junction (NMJ) of parasitic nematodes (roundworms). In susceptible worms, piperazine acts as a GABA (gamma-aminobutyric acid) receptor agonist. It binds to GABA receptors on the muscle cell membranes of the parasite, causing hyperpolarization of the muscle membrane. This hyperpolarization results in a flaccid paralysis of the worm, preventing it from maintaining its position in the host's intestinal lumen. The paralyzed worm is then dislodged and expelled from the gastrointestinal tract via normal peristalsis. Importantly, piperazine has no effect on the host's nervous system at therapeutic concentrations because it does not cross the blood-brain barrier to a significant extent and has relatively low affinity for mammalian GABA receptors compared to those of the parasite. In addition, piperazine is an ideal solvent for carbon dioxide (CO2) capture; the easy release of piperazine may be the reason for its relatively high CO2 absorption rate.
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| ln Vitro |
Piperazine (0.01-0.1 mM) slightly inhibits nematodes development compared to control. Piperazine (1 μM) reduces the total brood size of the nematodes. Piperazine increases the percentage of zebrafish with developmental delay in a dose-dependent manner[1]. Piperazine is attractive solvent for CO2 capture, and the facile Piperazine liberation may contribute to its relatively high CO2 absorption rate[2].
In vitro studies have characterized the anthelmintic effects of piperazine. Compared to control groups, piperazine at concentrations of 0.01-0.1 mM slightly inhibited the development of nematodes in culture. At 1 uM, piperazine reduced the total litter size of nematodes, indicating an effect on reproductive fitness. In zebrafish models, piperazine increased the proportion of developmentally delayed fish in a dose-dependent manner, reflecting the neurotoxic effects of the compound on lower vertebrates at high concentrations. Beyond its anti-parasitic role, piperazine has been extensively studied in the context of CO2 capture. It is considered an ideal CO2 capture solvent due to its high absorption rate and capacity. The easy release of piperazine may be the reason for its relatively high CO2 absorption rate compared to other amines. |
| ln Vivo |
In vivo activity of piperazine, particularly its anthelmintic effects, has been well-documented through decades of clinical use. In humans, a single oral dose of piperazine (typically 50-75 mg/kg) is effective in eliminating roundworm infections. The drug is poorly absorbed from the gastrointestinal tract (only 10-15% is absorbed), which concentrates its action at the site of infection. In veterinary medicine, piperazine has been widely used in livestock and companion animals to control nematode infections. In animal models, piperazine has been shown to cause worm paralysis and expulsion with a favorable safety margin. Studies in zebrafish have shown that piperazine increases the proportion of developmentally delayed fish in a dose-dependent manner, reflecting its potential neurotoxicity when systemically absorbed. However, these effects are typically not observed in mammals at therapeutic anthelmintic doses due to limited absorption and poor blood-brain barrier penetration.
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| Enzyme Assay |
Piperazine malate is not a receptor-binding compound in the traditional sense, but its GABA-ergic activity can be studied using electrophysiological or radioligand binding assays. A standard protocol for studying piperazine's mechanism of action would involve isolating Ascaris suum muscle strips. The muscle strip is suspended in an organ bath containing physiological saline solution at 37degC, bubbled with carbogen (95% O2, 5% CO2). A resting tension of approximately 1 g is applied. After an equilibration period, cumulative concentrations of piperazine (10 uM to 10 mM) are added to the bath, and the resulting muscle relaxation is recorded using an isometric force transducer. To confirm the involvement of GABA receptors, the muscle strips can be pre-incubated with a GABA receptor antagonist such as picrotoxin before the addition of piperazine; a rightward shift of the concentration-response curve would indicate competitive antagonism. For cell-free binding studies, worm membranes expressing GABA receptors can be prepared, and radiolabeled GABA displacement by piperazine can be measured.
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| Cell Assay |
Cellular assays for piperazine malate are not common, as piperazine's primary site of action is the parasite's neuromuscular junction, which is not easily represented by mammalian cell lines. However, cytotoxicity or viability studies in various cell lines (e.g., hepatocytes, intestinal epithelial cells) can be performed to assess safety. A standard protocol involves culturing cells in appropriate media (e.g., DMEM with 10% FBS) in 96-well plates. Upon reaching 80% confluence, cells are treated with varying concentrations of piperazine malate (e.g., 0.1 uM to 10 mM) for 24-72 hours. Cell viability is then quantified using an MTT assay. Additionally, for studies involving CO2 capture, piperazine solutions are analyzed using gas chromatography or NMR to determine CO2 loading capacity. For studies on nematode development, worms (e.g., Caenorhabditis elegans) are grown on agar plates seeded with E. coli. Piperazine is added to the culture medium, and endpoints such as growth rate, brood size, and developmental delay are assessed microscopically.
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| Animal Protocol |
In vivo animal experiments for piperazine-based anthelmintics are typically conducted in rodent models (e.g., mice infected with Heligmosomoides bakeri or Syphacia obvelata). A standard protocol: (1) Infect mice with a defined number of infective larvae (e.g., 200 L3 larvae of H. bakeri by oral gavage). (2) Allow the infection to establish for 14 days. (3) On day 14, weigh the mice and administer piperazine malate via oral gavage at a therapeutic dose (e.g., 50-75 mg/kg) suspended in a suitable vehicle such as distilled water or 0.5% carboxymethylcellulose (CMC). (4) Euthanize the mice 24-48 hours post-treatment. (5) Remove the small intestine and open it longitudinally. (6) Wash the intestinal contents over a sieve and count the number of adult worms present under a dissecting microscope. (7) Efficac is calculated as the percent reduction in worm count in the treated group compared to the vehicle control group. Histological examination of the intestine can also be performed to assess mucosal damage.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of piperazine are well-characterized from its historical use as a drug. After oral administration, piperazine is rapidly but incompletely absorbed from the gastrointestinal tract, with approximately 10-15% of the dose reaching systemic circulation. Peak plasma concentrations (Cmax) are typically achieved within 2-4 hours post-dose. The drug has a plasma half-life of approximately 2-4 hours in humans. Piperazine is poorly bound to plasma proteins (<20%). It is metabolized in the liver to a limited extent; the majority of the absorbed dose is excreted unchanged in the urine via glomerular filtration. Due to its small molecular weight (MW ~220 for the malate salt), piperazine can cross the placental barrier and is also excreted in breast milk. For piperazine malate specifically, the solubility is high in water (≥100 mg/mL, ~454.09 mM). The compound is stable as a powder for up to three years at -20degC and for six months in solution at -80degC.
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| Toxicity/Toxicokinetics |
The toxicity profile of piperazine has been established through clinical use. Acute overdose can lead to neurotoxic symptoms such as nausea, vomiting, blurred vision, muscle weakness, ataxia, and tremors, which are primarily due to excessive GABA receptor activation in the central nervous system. In rare cases, severe overdose may lead to seizures or coma. Chronic use or high doses may also cause urticaria (hives) and other hypersensitivity reactions. The LD50 in rodents is approximately 5-10 g/kg orally, indicating a relatively low acute lethality. Piperazine is generally contraindicated in patients with renal impairment because reduced excretion can lead to drug accumulation and increased neurotoxicity. In the form of piperazine malate, the malic acid component is generally recognized as safe (GRAS). Long-term carcinogenicity studies have not been conducted, but piperazine is not considered a potent carcinogen. The drug is embryotoxic in animal models at high doses, so it is generally avoided during pregnancy unless necessary.
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| References |
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| Additional Infomation |
Piperazine malate (CAS 14852-14-3) is a compound that exists as a white or off-white solid powder. The combination of piperazine (C4H10N2) and malic acid (C4H6O5) produces a salt that is stable at room temperature. The historical use of piperazine as an anthelmintic has largely been supplanted by newer, more potent drugs such as albendazole and mebendazole, which have a broader spectrum of activity and are effective as single-dose treatments. However, piperazine remains available in some countries for veterinary use. In research, piperazine continues to be studied for its chemical properties, particularly in the field of carbon capture. The "easy release" property of piperazine contributes to its high CO2 absorption rate compared to other amines, making it a topic of interest in green chemistry and environmental engineering. No ongoing clinical trials or FDA approvals exist for new indications for piperazine malate.
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| Molecular Formula |
C8H16N2O5
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| Molecular Weight |
220.22
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| Exact Mass |
220.106
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| CAS # |
14852-14-3
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| PubChem CID |
20510719
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| Appearance |
Solid Powder
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| Boiling Point |
428.7ºC at 760 mmHg
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| Flash Point |
213.1ºC
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| Vapour Pressure |
3.78E-09mmHg at 25°C
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| LogP |
0
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
15
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| Complexity |
155
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O([H])C([H])(C(=O)O[H])C([H])([H])C(=O)O[H].N1([H])C([H])([H])C([H])([H])N([H])C([H])([H])C1([H])[H]
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| InChi Key |
MGQUENZFJVXCFB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C4H10N2.C4H6O5/c1-2-6-4-3-5-1;5-2(4(8)9)1-3(6)7/h5-6H,1-4H2;2,5H,1H2,(H,6,7)(H,8,9)
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| Chemical Name |
2-hydroxybutanedioic acid;piperazine
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| Synonyms |
1,4-Diazacyclohexane malate
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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 |
| 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) |
H2O : ≥ 100 mg/mL (~454.09 mM)
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.5409 mL | 22.7046 mL | 45.4091 mL | |
| 5 mM | 0.9082 mL | 4.5409 mL | 9.0818 mL | |
| 10 mM | 0.4541 mL | 2.2705 mL | 4.5409 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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