| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
The primary targets of pivagabine involve the GABAA receptor and the corticotropin-releasing factor (CRF) system. Research demonstrates that this compound antagonizes stress-induced changes in GABAA receptor function, as evidenced by inhibition of foot shock-induced increases in [35S]TBPS binding to unwashed brain membranes. Additionally, pivagabine modulates brain CRF concentrations, preventing stress-induced decreases of CRF in the hypothalamus (74%) and increases in the cerebral cortex (125%).
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| ln Vitro |
In vitro activity data for pivagabine are relatively limited. As an amino acid derivative, the compound‘s in vitro activity likely involves modulation of neurotransmitter systems. Pivagabine has been shown to penetrate the blood-brain barrier (BBB) in in vitro studies, a critical prerequisite for its central nervous system activity.
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| ln Vivo |
One hour prior to sacrifice on day five, ivagabine (CXB 722) (200 mg/kg; intraperitoneal; twice daily for four days) inhibits the impact of foot impact stress on CRF concentrations in both brain regions [2].
Pivagabine exhibits significant neuromodulatory and antistress activity in vivo. In a foot shock stress model in male rats, subchronic treatment with pivagabine (100-200 mg/kg, IP) dose-dependently inhibited stress-induced alterations in GABAA receptor function. The compound prevented stress-induced decreases in hypothalamic CRF concentrations (74%) and increases in cerebral cortex CRF levels (125%). Pivagabine alone reduced hypothalamic CRF concentration by 52% but had no effect on the cerebral cortex. Additionally, behavioral studies demonstrated that the compound prevented pentylenetetrazol- and bicuculline-induced convulsions in rats and reduced physical and mental fatigability in neurasthenia patients. |
| Enzyme Assay |
The effect of pivagabine on GABAA receptors can be assessed using radioligand binding assays. A classic experimental protocol is as follows: Prepare unwashed membranes from rat cerebral cortex, incubate the membranes with [35S]t-butylbicyclophosphorothionate ([35S]TBPS, a radiolabeled ligand for the GABA-gated chloride channel) in buffer containing serial concentrations of pivagabine at 25°C for 90 minutes. After incubation, separate bound and free ligands by rapid vacuum filtration through glass fiber filters and measure radioactivity using a scintillation counter. The stress-induced increase in [35S]TBPS binding is antagonized by pivagabine pretreatment.
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| Cell Assay |
Using neuronal cell lines such as SH-SY5Y or PC12 cells, cell viability can be assessed via MTT/CCK-8 assays to evaluate cytotoxicity, and signaling pathway effects can be studied by measuring intracellular cAMP levels or calcium influx.
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| Animal Protocol |
Animal/Disease Models: Adult male SD (SD (Sprague-Dawley)) CD rat (200-250 g) [2]
Doses: 200 mg/kg Route of Administration: intraperitoneal (ip) injection; twice (two times) daily for 4 days, results 1 hour before sacrifice on day 5 Experimental Results: Preventing the effects of foot impact stress on CRF concentrations in two brain regions. The CRF concentration in the hypothalamus was diminished by 52%, but had no effect on the CRF concentration in the cerebral cortex. The antistress activity of pivagabine can be evaluated using a rat foot shock stress model. A classic experimental protocol is as follows: Use adult male Sprague-Dawley CD rats (200-250 g). Administer pivagabine at 200 mg/kg intraperitoneally, twice daily for 4 days, with an additional dose 1 hour before sacrifice on day 5. Stress induction: Place rats in cages equipped with a metal grid floor and deliver foot shock stress immediately before sacrifice. At the experimental endpoint after sacrifice, dissect hypothalamus and cerebral cortex tissues, extract CRF for radioimmunoassay (RIA) quantification, and prepare brain membranes for [35S]TBPS binding measurement. |
| ADME/Pharmacokinetics |
The pharmacokinetic profile of pivagabine includes good oral bioavailability and the ability to penetrate the blood-brain barrier in animals. In rats, the compound does not undergo significant metabolic transformation. Population pharmacokinetic modeling estimates an apparent volume of distribution of approximately 40 L and clearance of approximately 15 L/h. The elimination half-life of pivagabine is approximately 6.4 hours based on published data. The pKa values are 4.45 (acidic) and 12.63 (acidic), suggesting that the compound exists predominantly in dissociated form at physiological pH. The compound is administered orally, and a regimen of 900 mg twice daily has been used in human trials.
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| Toxicity/Toxicokinetics |
Toxicological evaluations indicate that pivagabine exhibits a low toxicity profile following either single or repeated administration. No significant toxic effects were observed in animal studies, but long-term safety data in humans are limited. According to the DrugBank database, pivagabine may have interactions with various central nervous system drugs (including benzodiazepines, antipsychotics, and antidepressants), potentially increasing the risk of CNS depression. The drug was discontinued in Italy after 1999 due to market factors rather than safety concerns.
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| References | |
| Additional Infomation |
Pitavabine is an oxygen- and nitrogen-containing organic compound whose function is related to γ-amino acids. Pitavabine has been used in clinical trials investigating the treatment of stress and anxiety.
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| Molecular Formula |
C9H17NO3
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|---|---|
| Molecular Weight |
187.236182928085
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| Exact Mass |
187.121
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| CAS # |
69542-93-4
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| PubChem CID |
68888
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| Appearance |
White to off-white solid powder
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| Density |
1.053g/cm3
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| Boiling Point |
397ºC at 760 mmHg
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| Flash Point |
193.9ºC
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| Index of Refraction |
1.462
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| LogP |
1.853
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
13
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| Complexity |
194
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C(C)(C)C)NCCCC(=O)O
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| InChi Key |
SRPNQDXRVRCTNK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C9H17NO3/c1-9(2,3)8(13)10-6-4-5-7(11)12/h4-6H2,1-3H3,(H,10,13)(H,11,12)
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| Chemical Name |
4-(2,2-dimethylpropanoylamino)butanoic acid
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| Synonyms |
Pivagabine; CXB-722; CXB 722; 69542-93-4; Pivagabina; CXB722;
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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) |
DMSO : ~50 mg/mL (~267.04 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (13.35 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 (13.35 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (13.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.3407 mL | 26.7037 mL | 53.4074 mL | |
| 5 mM | 1.0681 mL | 5.3407 mL | 10.6815 mL | |
| 10 mM | 0.5341 mL | 2.6704 mL | 5.3407 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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