Ethosuximide
(Synonyms: 乙琥胺) 目录号 : GC33695
An anticonvulsant
Cas No.:77-67-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | Vehicle- and Ethosuximide-treated Tau V337M worms are lysed and separated into soluble and insoluble fractions. Fractions are separated by SDS-PAGE and western blotted using anti-human Tau T46 and anti-actin antibodies. The abundance of Tau protein in each fraction is quantified by densitometry and normalized against beta-actin. Total Tau levels in lysates are expressed as the percentage of actin-normalized Tau relative to vehicle control lysates; Tau levels in sequentially extracted fractions are expressed as the percentage of actin-normalized Tau relative to the sum of both fractions (soluble+RIPA) combined[1]. |
Cell experiment: | Neuronal stem cells from the forebrain Cortex of a 3-day-old rat are used in this study. The cells are differentiated by withdrawal of basic fibroblastic growth factor (bFGF) and exposed to Ethosuximide at two concentrations of 0.1 μM and 1 μM. Before drug treatment, the cells are rinsed once with PBS, and the medium is replaced with fresh, bFGF-free DMEM/F12 medium containing different concentration of Ethosuximide. Medium exchange is done every day for 6 days with medium containing Ethosuximide. Then, cells are fixed for immunocytochemistry[2]. |
References: [1]. Chen X, et al. Ethosuximide ameliorates neurodegenerative disease phenotypes by modulating DAF-16/FOXO target gene expression. Mol Neurodegener. 2015 Sep 29;10:51. | |
Ethosuximide is an anticonvulsant.1,2,3,4,5 It increases glucose, fructose-1,6-bisphosphate, and pyruvate levels in rat brain when administered at a dose of 200 mg/kg.1 Ethosuximide (400 mg/kg) reduces the severity of audiogenic seizures in a rat model of barbiturate withdrawal-induced convulsions.2 It also inhibits tonic hindlimb extension induced by pentylenetetrazole or brainstem stimulation (ED50s = 35 and 70 mg/kg, respectively), as well as leptazol-induced clonic seizures (ED50 = 230 mg/kg), in rats.3,4 Ethosuximide reduces resting tremor by 60% in a macaque model of Parkinson's disease induced by MPTP when administered at a dose of 150 mg/animal for 5 days.5 Formulations containing ethosuximide have been used in the treatment of petit mal seizures.
1.Nahorski, S.R.Biochemical effects of the anticonvulsants trimethadione, ethosuximide and chlordiazepoxide in rat brainJ. Neurochem.19(8)1937-1946(1972) 2.Norton, P.R.The effects of drugs on barbiturate withdrawal convulsions in the ratJ. Pharm. Pharmacol.22(10)763-766(1970) 3.Consroe, P.F., and Wolkin, A.L.Anticonvulsant interaction of cannabidiol and ethosuximide in ratsJ. Pharm. Pharmacol.29(8)500-501(1977) 4.Chiu, P., and Burnham, W.M.The effect of anticonvulsant drugs on convulsions triggered by direct stimulation of the brainstemNeuropharmacology21(4)355-359(1982) 5.Gomez-Mancilla, B., Latulippe, J.F., Boucher, R., et al.Effect of ethosuximide on rest tremor in the MPTP monkey modelMov. Disord.7(2)137-141(1992)
| Cas No. | 77-67-8 | SDF | |
| 别名 | 乙琥胺 | ||
| Canonical SMILES | O=C(C(C)(CC)C1)NC1=O | ||
| 分子式 | C7H11NO2 | 分子量 | 141.17 |
| 溶解度 | DMSO : ≥ 125 mg/mL (885.46 mM) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 7.0837 mL | 35.4183 mL | 70.8366 mL |
| 5 mM | 1.4167 mL | 7.0837 mL | 14.1673 mL |
| 10 mM | 0.7084 mL | 3.5418 mL | 7.0837 mL |
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Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy
N Engl J Med 2010 Mar 4;362(9):790-9.PMID:20200383DOI:10.1056/NEJMoa0902014.
Background: Childhood absence epilepsy, the most common pediatric epilepsy syndrome, is usually treated with Ethosuximide, valproic acid, or lamotrigine. The most efficacious and tolerable initial empirical treatment has not been defined. Methods: In a double-blind, randomized, controlled clinical trial, we compared the efficacy, tolerability, and neuropsychological effects of Ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug doses were incrementally increased until the child was free of seizures, the maximal allowable or highest tolerable dose was reached, or a criterion indicating treatment failure was met. The primary outcome was freedom from treatment failure after 16 weeks of therapy; the secondary outcome was attentional dysfunction. Differential drug effects were determined by means of pairwise comparisons. Results: The 453 children who were randomly assigned to treatment with Ethosuximide (156), lamotrigine (149), or valproic acid (148) were similar with respect to their demographic characteristics. After 16 weeks of therapy, the freedom-from-failure rates for Ethosuximide and valproic acid were similar (53% and 58%, respectively; odds ratio with valproic acid vs. Ethosuximide, 1.26; 95% confidence interval [CI], 0.80 to 1.98; P=0.35) and were higher than the rate for lamotrigine (29%; odds ratio with Ethosuximide vs. lamotrigine, 2.66; 95% CI, 1.65 to 4.28; odds ratio with valproic acid vs. lamotrigine, 3.34; 95% CI, 2.06 to 5.42; P<0.001 for both comparisons). There were no significant differences among the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with Ethosuximide (in 49% of the children vs. 33%; odds ratio, 1.95; 95% CI, 1.12 to 3.41; P=0.03). Conclusions: Ethosuximide and valproic acid are more effective than lamotrigine in the treatment of childhood absence epilepsy. Ethosuximide is associated with fewer adverse attentional effects. (ClinicalTrials.gov number, NCT00088452.)
Ethosuximide: from bench to bedside
CNS Drug Rev 2007 Summer;13(2):224-39.PMID:17627674DOI:10.1111/j.1527-3458.2007.00009.x.
Ethosuximide, 2-ethyl-2-methylsuccinimide, has been used extensively for "petit mal" seizures and it is a valuable agent in studies of absence epilepsy. In the treatment of epilepsy, Ethosuximide has a narrow therapeutic profile. It is the drug of choice in the monotherapy or combination therapy of children with generalized absence (petit mal) epilepsy. Commonly observed side effects of Ethosuximide are dose dependent and involve the gastrointestinal tract and central nervous system. Ethosuximide has been associated with a wide variety of idiosyncratic reactions and with hematopoietic adverse effects. Typical absence seizures are generated as a result of complex interactions between the thalamus and the cerebral cortex. This thalamocortical circuitry is under the control of several specific inhibitory and excitatory systems arising from the forebrain and brainstem. Corticothalamic rhythms are believed to be involved in the generation of spike-and-wave discharges that are the characteristic electroencephalographic signs of absence seizures. The spontaneous pacemaker oscillatory activity of thalamocortical circuitry involves low threshold T-type Ca2+ currents in the thalamus, and Ethosuximide is presumed to reduce these low threshold T-type Ca2+ currents in thalamic neurons. Ethosuximide also decreases the persistent Na+ and Ca2+ -activated K+ currents in thalamic and layer V cortical pyramidal neurons. In addition, there is evidence that in a genetic absence epilepsy rat model Ethosuximide reduces cortical gamma-aminobutyric acid (GABA) levels. Also, elevated glutamate levels in the primary motor cortex of rats with absence epilepsy (but not in normal animals) are reduced by Ethosuximide.
Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents
Cochrane Database Syst Rev 2017 Feb 14;2(2):CD003032.PMID:28195639DOI:10.1002/14651858.CD003032.pub3.
Background: This is an updated version of the original Cochrane review originally published in 2003, Issue 3, and updated in 2005, Issue 4.Absence seizures are brief epileptic seizures which present in childhood and adolescence. Depending on clinical features and electroencephalogram (EEG) findings they are divided into typical, atypical absences, and absences with special features. Typical absences are characterised by sudden loss of awareness and an EEG typically shows generalised spike wave discharges at three cycles per second. Ethosuximide, valproate and lamotrigine are currently used to treat absence seizures. This review aims to determine the best choice of antiepileptic drug for children and adolescents with typical absence seizures. Objectives: To review the evidence for the effects of Ethosuximide, valproate and lamotrigine as treatments for children and adolescents with absence seizures, when compared with placebo or each other. Search methods: We searched the Cochrane Epilepsy Group's Specialized Register (1 September 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 1 September 2016), MEDLINE (Ovid, 1946 to 1 September 2016), ClinicalTrials.gov (1 September 2016) and the WHO International Clinical Trials Registry Platform ICTRP (1 September 2016). Previously we searched Embase (1988 to March 2005) and SCOPUS (1823 to 31 March 2014). No language restrictions were imposed. In addition, we contacted Sanofi Winthrop, Glaxo Wellcome (now GlaxoSmithKline) and Parke Davis (now Pfizer), manufacturers of sodium valproate, lamotrigine and Ethosuximide respectively. Selection criteria: Randomised parallel group monotherapy or add-on trials which include a comparison of any of the following in children or adolescents with absence seizures: Ethosuximide; sodium valproate; lamotrigine; or placebo. Data collection and analysis: Outcome measures were: (1) proportion of individuals seizure free at one, three, six, 12 and 18 months post randomisation; (2) people with a 50% or greater reduction in seizure frequency; (3) normalisation of EEG and/or negative hyperventilation test; and (4) adverse effects. Data were independently extracted by two review authors. Results are presented as risk ratios (RR) with 95% confidence intervals (95% CIs). Main results: Eight small trials were found (three of them not included in the previous version of the review). Six of them were of poor methodological quality and seven recruited less than 50 participants. There are no placebo-controlled trials for Ethosuximide or valproate, and hence, no evidence from randomised controlled trials to support a specific effect on absence seizures for either of these two drugs. Due to the differing methodologies used in the trials comparing Ethosuximide, lamotrigine and valproate, we thought it inappropriate to undertake a meta-analysis. One large randomised, parallel double-blind controlled trial comparing Ethosuximide, lamotrigine and sodium valproate in children with newly diagnosed childhood absence epilepsy found that at 12 months, the freedom-from-failure rates for Ethosuximide and valproic acid (VPA) were similar and were higher than the rate for lamotrigine. The frequency of treatment failures due to lack of seizure control (P < 0.001) and intolerable adverse events (P < 0.037) was significantly different among the treatment groups, with the largest proportion of lack of seizure control in the lamotrigine cohort, and the largest proportion of adverse events in the VPA group. Overall, this large study demonstrates the superior effectiveness of Ethosuximide and VPA compared to lamotrigine as initial monotherapy aimed to control seizures without intolerable adverse effects in children with childhood absence epilepsy. Authors' conclusions: With regards to both efficacy and tolerability, Ethosuximide represents the optimal initial empirical monotherapy for children and adolescents with absence seizures. However, if absence and generalised tonic-clonic seizures coexist, valproate should be preferred, as Ethosuximide is probably inefficacious on tonic-clonic seizures.
The metabolism of Ethosuximide
Eur J Drug Metab Pharmacokinet 1993 Oct-Dec;18(4):349-53.PMID:8020533DOI:10.1007/BF03190184.
The metabolism of the antiepileptic drug Ethosuximide (3-ethyl-3-methylpyrollidine-2,5-dione) (I) in animals and humans is reviewed. Chiral aspects of the metabolism of Ethosuximide are discussed. Clarification of the precise nature of the hydroxymetabolites of Ethosuximide is presented.
Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents
Cochrane Database Syst Rev 2005 Oct 19;(4):CD003032.PMID:16235312DOI:10.1002/14651858.CD003032.pub2.
Background: Absence seizures are brief epileptic seizures which present in childhood and adolescence. They are characterised by sudden loss of awareness and an electroencephalogram (EEG) typically shows generalised spike wave discharges at three cycles per second. Ethosuximide, valproate and lamotrigine are currently used to treat absence seizures. This review aims to determine the best choice of anticonvulsant for a child with typical absence seizures. Objectives: To review the evidence for the effects of Ethosuximide, valproate and lamotrigine as treatments for children and adolescents with absence seizures, when compared with placebo or each other. Search strategy: We searched the Cochrane Epilepsy Group's Specialised Register (March 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to March 2005) and EMBASE (1988 to March 2005). No language restrictions were imposed. In addition, we contacted Sanofi Winthrop, Glaxo Wellcome (now GlaxoSmithKline) and Parke Davis (now Pfizer), manufacturers of sodium valproate, lamotrigine and Ethosuximide respectively. Selection criteria: Randomised parallel group monotherapy or add-on trials which include a comparison of any of the following in children or adolescents with absence seizures: Ethosuximide; sodium valproate; lamotrigine or placebo. Data collection and analysis: Outcome measures were: (1) proportion of individuals seizure free at 1, 3, 6, 12 and 18 months post randomisation; (2) people with a 50% or greater reduction in seizure frequency; (3) normalisation of EEG and/or negative hyperventilation test and (4) adverse effects. Data were independently extracted by two review authors. Results are presented as relative risks (RR) with 95% confidence intervals (95% CI). Main results: Five small trials were found, four of them were of poor methodological quality. One trial (29 participants) compared lamotrigine with placebo using a response conditional design. Individuals taking lamotrigine were significantly more likely to be seizure free than participants taking placebo during this short trial. Another trial compared lamotrigine with sodium valproate, the study lacked power to detect the difference in efficacy. Three studies compared Ethosuximide, but because of diverse study designs and populations studied, we decided not to pool results in a meta-analysis. None of these studies found a difference between valproate and Ethosuximide with respect to seizure control, but confidence intervals were wide and the existence of important differences could not be excluded. Authors' conclusions: Although Ethosuximide, lamotrigine and valproate are commonly used to treat people with absence seizures we have insufficient evidence to inform clinical practice, and the few trials included in this review were of poor methodological quality and did not have sufficient number of participants. More trials of better quality are needed.