| Size | Price | Stock | Qty |
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| 10mg |
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| Targets |
Progabide targets GABA receptors, specifically GABAA and GABAB receptors. As a prodrug, it is metabolized to GABA, which then binds to and activates these receptors. Activation of GABAA receptors increases chloride influx, hyperpolarizing the neuron and reducing neuronal excitability. Activation of GABAB receptors modulates potassium channels and reduces calcium influx, also reducing neuronal excitability. The compound's anticonvulsant effects are mediated through enhanced GABAergic inhibition.
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| ln Vitro |
In vitro, progabide and its metabolites bind to GABA receptors and enhance GABAergic neurotransmission. Its activity is assessed using radioligand binding assays, where the compound or its metabolites displace radiolabeled GABA receptor ligands. Functional assays measure GABA receptor-mediated chloride flux or changes in membrane potential in neuronal cultures. The compound's anticonvulsant activity has been demonstrated in various in vitro seizure models.
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| ln Vivo |
An agonist of the gamma-aminobutyric acid receptor (GABA) is progabide. When Progabide was injected intraperitoneally at 50, 100, and 200 mg/kg, the corresponding increases in plasma corticosterone levels were 244, 365, and 476% (t=6.44 to 12.55, p<0.01). The dose of progabide (10 mg/kg) had no effect on plasma corticosterone levels (t=0.76, NS). Increases in plasma corticosterone levels at 30 minutes (t=2.625, p<0.05), 60 minutes (t=13.13, p<0.001), and 120 minutes (t=4.07, p<0.01) were significantly produced by 200 mg/kg Progabide. pharmacological injection, but 240 minutes later (t=0.86, NS), the values went back to control. Progabide is administered for 60 minutes to achieve the maximum corticosterone rise (in comparison to matched controls) [1].
In vivo, progabide has been studied for its anticonvulsant effects in animal models of epilepsy. It has shown efficacy in various seizure models, including maximal electroshock, pentylenetetrazol-induced seizures, and kindling models. The compound has also been investigated for its potential in other neurological disorders, including spasticity and anxiety. Clinical studies have evaluated its efficacy in epilepsy patients, but its development was limited due to side effects and variable efficacy. |
| Enzyme Assay |
The in vitro activity of progabide is assessed using receptor binding assays and electrophysiological techniques. For GABA receptor binding, membrane preparations from brain tissue or cells expressing GABA receptors are incubated with a radiolabeled GABA receptor ligand (e.g., [³H]muscimol for GABAA, [³H]baclofen for GABAB) in the presence of varying concentrations of progabide or its metabolites. The displacement of the radiolabeled ligand is measured. For functional assays, patch-clamp electrophysiology is used to measure GABA receptor-mediated currents in neurons treated with progabide.
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| Cell Assay |
For cellular assays, primary neuronal cultures or neuronal cell lines are used. Cells are cultured in appropriate media and treated with various concentrations of progabide (typically 1-1000 μM) for defined periods. GABA receptor-mediated chloride influx can be measured using a fluorescence-based chloride-sensitive dye (e.g., MQAE). Membrane potential changes can be assessed using voltage-sensitive dyes. Cell viability is assessed using standard assays.
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| Animal Protocol |
In vivo, progabide is typically administered orally or intraperitoneally to animal models. In seizure models, the compound is administered at various doses (typically 10-100 mg/kg), and seizure activity is monitored. In maximal electroshock models, seizure duration and severity are assessed. In pentylenetetrazol models, the latency to seizure onset and seizure score are recorded. In kindling models, the progression of seizure severity is monitored over time.
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
Absorbed well, with a bioavailability of 60%. Metabolism/Metabolites Hepatic Biological Half-Life 4 hours Progabide has a molecular weight of 334.77 g/mol and a molecular formula of C17H16ClFN2O2. It is a lipophilic compound that can cross the blood-brain barrier. The compound is a prodrug that is metabolized to GABA and other active metabolites. Specific pharmacokinetic parameters such as bioavailability, half-life, and metabolism are not detailed in the provided search results. The compound should be stored under appropriate conditions to maintain stability. |
| Toxicity/Toxicokinetics |
Protein Binding
95% Progabide can cause side effects including sedation, dizziness, gastrointestinal disturbances, and hepatotoxicity. The compound has been associated with liver enzyme elevations and, in some cases, liver failure, which limited its clinical use. Other side effects may include drowsiness, ataxia, and confusion. The compound should be used with caution in patients with liver disease. Comprehensive toxicological studies are required to establish its full safety profile. |
| References | |
| Additional Infomation |
Progabide is a diarylmethane compound. It is an analogue and prodrug of γ-aminobutyric acid (GABA). It is commonly used to treat epilepsy. It has agonistic activity against both GABAA and GABAB receptors. In clinical trials, Progabide has been used to treat Parkinson's disease, schizophrenia, clinical depression, and anxiety disorders; however, its efficacy in these diseases is not fully elucidated.
Drug Indications Indications for the treatment of epilepsy. Mechanism of Action Progabide binds to GABAA and GABAB receptors located at the terminals of primary afferent fibers. Binding to GABAA receptors leads to increased affinity of GABA receptors for amino acids, increased chloride ion flux across the terminal membrane, and enhanced presynaptic inhibition. Activation of GABAB receptors delays calcium ion inflow into the terminal, thereby reducing the release of excitatory amino acids and other neurotransmitters. Pharmacodynamics Propapamine is a fatty acid derivative, belonging to the GABA receptor agonist class, and is used to treat epilepsy symptoms. Progabide is an antiepileptic agent that was developed as a prodrug for GABA. It was one of the first GABA prodrugs to be studied clinically for the treatment of epilepsy. However, its development was limited due to hepatotoxicity and variable efficacy. The compound is not commonly used clinically and is primarily of research interest. Progabide is available from chemical suppliers for research purposes. |
| Molecular Formula |
C17H16CLFN2O2
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| Molecular Weight |
334.77
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| Exact Mass |
334.088
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| CAS # |
62666-20-0
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| PubChem CID |
44115
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3g/cm3
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| Boiling Point |
525.363ºC at 760 mmHg
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| Melting Point |
133-135°; mp 142.5° (Kaplan, J. Med. Chem.)
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| Flash Point |
271.53ºC
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| Index of Refraction |
1.59
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| LogP |
3.987
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
23
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| Complexity |
425
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IBALRBWGSVJPAP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H16ClFN2O2/c18-12-5-3-11(4-6-12)17(21-9-1-2-16(20)23)14-10-13(19)7-8-15(14)22/h3-8,10,22H,1-2,9H2,(H2,20,23)
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| Chemical Name |
4-[[(4-chlorophenyl)-(5-fluoro-2-hydroxyphenyl)methylidene]amino]butanamide
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| Synonyms |
Gabrene; Halogabide; Progabide
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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 : ~250 mg/mL (~746.78 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 | 2.9871 mL | 14.9356 mL | 29.8713 mL | |
| 5 mM | 0.5974 mL | 2.9871 mL | 5.9743 mL | |
| 10 mM | 0.2987 mL | 1.4936 mL | 2.9871 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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