| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
Phensuximide targets T-type calcium channels in the thalamus, which are believed to play a critical role in the generation of the spike-and-wave discharges characteristic of absence seizures. By blocking these channels, Phensuximide reduces the abnormal oscillatory activity in the thalamocortical circuitry, thereby suppressing the seizures. Phensuximide is an anticonvulsant in the succinimide class. It suppresses the paroxysmal three-cycle-per-second spike and wave EEG pattern associated with lapses of consciousness in petit mal seizures. The frequency of attacks is reduced by depression of nerve transmission in the motor cortex.
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| ln Vitro |
In incubated slices of mouse cerebral cortex, phensuximide causes depolarization-induced buildup of cyclic GMP or cyclic AMP levels with ID50 values of 8.00 mM or 6.20 mM [2]. With Ki and Km values of 559 μM and 235 μM, respectively, phensuximide (0.5-2.0 mM) can competitively inhibit the activity of mephenytoin 4-hydroxylase in human liver microsomes [4].
In vitro studies have characterized Phensuximide as an anticonvulsant that suppresses spike-and-wave EEG patterns. Its effects on T-type calcium channels have been studied using electrophysiological techniques. Phensuximide has been shown to inhibit T-type calcium currents in thalamic neurons, which is believed to be the mechanism underlying its anticonvulsant activity. These in vitro studies confirm that Phensuximide is a potent inhibitor of T-type calcium channels. |
| ln Vivo |
In Sprague-Dawley rats, phensuximide (intraperitoneal injection; 1.25 mmol/kg; single dosage) mildly alters renal function by increasing proteinuria, decreasing paraaminohippuric acid absorption, and producing microhematuria [1]. Hematuria and proteinuria were temporary side effects of fenximide (intraperitoneal injection; 0.3 or 0.6 mmol/kg; 5-7 days); other renal function measures were unaffected. It was determined that Fischer 344 rats, an appropriate model for researching phenximide-induced urinary tract toxicity, exhibit modest, temporary renal effects when exposed to phenximide [1].
In vivo studies have demonstrated that Phensuximide is effective in reducing the frequency of absence seizures. It suppresses the paroxysmal three-cycle-per-second spike and wave EEG pattern associated with lapses of consciousness in petit mal seizures. The frequency of attacks is reduced by depression of nerve transmission in the motor cortex. Phensuximide has been used clinically for the treatment of absence seizures. Its efficacy has been established in clinical studies. |
| Enzyme Assay |
The in vitro assays for Phensuximide measure its effects on T-type calcium channels. Electrophysiological techniques, such as patch-clamp, are used to measure T-type calcium currents in thalamic neurons or in heterologous expression systems. The inhibition of T-type calcium currents by Phensuximide is measured, and the IC50 is determined. These assays confirm that Phensuximide is an inhibitor of T-type calcium channels.
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| Cell Assay |
In vitro cell-based assays for Phensuximide are not typically performed, as the compound's primary mechanism of action is through the modulation of ion channels rather than direct effects on cells. However, the compound's effects on neuronal excitability can be studied using neuronal cultures or brain slices. These assays measure the ability of Phensuximide to reduce neuronal firing or to suppress epileptiform activity.
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| Animal Protocol |
Animal/Disease Models: Fischer 344 rat[1]
Doses: 0.3 or 0.6 mmol/kg Route of Administration: intraperitoneal (ip) injection; 5-7 days Experimental Results: Fischer 344 rats induced urinary tract toxicity after daily administration for 5-7 days. In vivo animal experiments for Phensuximide are conducted in animal models of absence seizures. In a typical study, Phensuximide is administered to rodents, and EEG recordings are performed to assess the suppression of spike-and-wave discharges. The compound's ability to reduce seizure frequency and duration is assessed. These studies provide evidence for the in vivo efficacy of Phensuximide as an anticonvulsant. |
| ADME/Pharmacokinetics |
Absorption, distribution, and excretion are rapid and complete. Metabolism/Metabolites are produced by the liver.
Phensuximide has a molecular weight of 189.21 g/mol and a molecular formula of C11H11NO2. It is a solid compound with a purity of ≥95%. It is slightly soluble in water (about 4.2 mg/ml at 25°C) and readily soluble in methanol and ethanol. It forms fine crystals from hot 95% ethanol, with a melting point of 71-73°C. For storage, it is recommended to keep the powder at -20°C for up to 3 years. Pharmacokinetic properties have been studied, and Phensuximide is absorbed after oral administration. |
| Toxicity/Toxicokinetics |
Protein Binding
21% Phensuximide is an approved drug and its safety profile has been established in clinical use. Common side effects of succinimide anticonvulsants include gastrointestinal disturbances, drowsiness, dizziness, and headache. Rare but serious side effects include blood dyscrasias and hypersensitivity reactions. Phensuximide is contraindicated in patients with hypersensitivity to succinimides. As with all drugs, it should be used under medical supervision. For research use, standard laboratory safety precautions should be followed when handling Phensuximide. |
| References | |
| Additional Infomation |
Phenylsuximide belongs to the pyrrolidine class of drugs. It is a succinimide class of drugs with anticonvulsant properties. It inhibits the paroxysmal three-cycle-per-second spike-and-wave EEG pattern associated with loss of consciousness in absence seizures. By inhibiting neural conduction in the motor cortex, it can reduce the frequency of seizures. Indications: Used for the treatment of epilepsy. Mechanism of Action: The mechanism of action of phenylsuximide is not fully understood, but it may act on the inhibitory neuronal system crucial for the generation of the three-cycle-per-second rhythm. Its effect may be related to its ability to inhibit the accumulation of depolarization-induced cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in brain tissue.
Phensuximide is an approved drug for the treatment of absence seizures (petit mal seizures). It is an anticonvulsant in the succinimide class. Phensuximide suppresses the paroxysmal three-cycle-per-second spike and wave EEG pattern associated with lapses of consciousness. The frequency of attacks is reduced by depression of nerve transmission in the motor cortex. Its mechanism of action involves the inhibition of T-type calcium channels in the thalamus, which reduces the abnormal oscillatory activity underlying absence seizures. Phensuximide is used clinically and as a research tool to study epilepsy and anticonvulsant mechanisms. |
| Molecular Formula |
C11H11NO2
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| Molecular Weight |
189.21
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| Exact Mass |
189.079
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| CAS # |
86-34-0
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| PubChem CID |
6839
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| Appearance |
White to off-white solid powder
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| Density |
1.1596 (rough estimate)
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| Boiling Point |
324.47°C (rough estimate)
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| Melting Point |
71-73°
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| Index of Refraction |
1.5012 (estimate)
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| LogP |
1.096
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
14
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| Complexity |
256
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1CC(C2C=CC=CC=2)C(=O)N1C
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| InChi Key |
WLWFNJKHKGIJNW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H11NO2/c1-12-10(13)7-9(11(12)14)8-5-3-2-4-6-8/h2-6,9H,7H2,1H3
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| Chemical Name |
1-methyl-3-phenylpyrrolidine-2,5-dione
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| Synonyms |
Milontin LifenePhensuximide Succitimal phensuximide, (+-)-isomerPhenylsuximide Epimid
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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 (~1321.28 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 | 5.2851 mL | 26.4257 mL | 52.8513 mL | |
| 5 mM | 1.0570 mL | 5.2851 mL | 10.5703 mL | |
| 10 mM | 0.5285 mL | 2.6426 mL | 5.2851 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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