Synonym
Ethosuximide; Etosuximida; Ethosuxide; Emeside; Ethosuccimid; Ethosuximide; Ethylmethylsuccimide; Ethymal; Zarontin; CI-366; CI366; CI 366; NSC 64013; NSC64013; NSC-64013;
IUPAC/Chemical Name
3-Ethyl-3-methyl-2,5-pyrrolidinedione
InChi Key
HAPOVYFOVVWLRS-UHFFFAOYSA-N
InChi Code
InChI=1S/C7H11NO2/c1-3-7(2)4-5(9)8-6(7)10/h3-4H2,1-2H3,(H,8,9,10)
SMILES Code
O=C(C(C)(CC)C1)NC1=O
Appearance
White to off-white crystalline powder.
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Ethosuximide improves the phenotypes of multiple neurodegenerative disease models and blocks the low voltage activated T-type calcium channel.
In vitro activity:
Ethosuximide at clinically relevant concentrations inhibited GIRK channels expressed in Xenopus oocytes. The inhibition was concentration-dependent, but voltage-independent, and time-independent during each voltage pulse.
Reference: Neuropharmacology. 2009 Feb;56(2):499-506. https://pubmed.ncbi.nlm.nih.gov/18977371/
In vivo activity:
Intraperitoneal pre-treatment (30 min prior) of mice with ethosuximide (10.0–30.0 mg/kg) produced a dose-dependent inhibition of itch responses in male (Fig. 1a) and female (Fig. 1b) mice injected with histamine. Ethosuximide was also able to decrease the time mice spent scratching when co-delivered subcutaneously (100.0–1000.0 μg) with histamine in either male (Fig. 1c) or female (Fig. 1d) mice. Similarly, systemically delivered ethosuximide (10.0–30.0 mg/kg) elicited dose-dependent inhibition of scratching behaviour of male (Fig. 2a) and female (Fig. 2b) subjects that received chloroquine diphosphate. Likewise, ethosuximide produced a significant reduction of itch responses when co-delivered (100.0–1000.0 μg) with chloroquine in male (Fig. 2c) and female (Fig. 2d).
Reference: Mol Brain. 2021; 14: 46. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927410/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
64.0 |
453.36 |
| Ethanol |
28.0 |
198.35 |
| Water |
28.0 |
198.35 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
141.17
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Kobayashi T, Hirai H, Iino M, Fuse I, Mitsumura K, Washiyama K, Kasai S, Ikeda K. Inhibitory effects of the antiepileptic drug ethosuximide on G protein-activated inwardly rectifying K+ channels. Neuropharmacology. 2009 Feb;56(2):499-506. doi: 10.1016/j.neuropharm.2008.10.003. Epub 2008 Oct 17. PMID: 18977371.
2. Gadotti VM, Zamponi GW. Ethosuximide inhibits acute histamine- and chloroquine-induced scratching behavior in mice. Mol Brain. 2021 Mar 2;14(1):46. doi: 10.1186/s13041-021-00762-1. PMID: 33653383; PMCID: PMC7927410.
3. Kerckhove N, Boudieu L, Ourties G, Bourdier J, Daulhac L, Eschalier A, Mallet C. Ethosuximide improves chronic pain-induced anxiety- and depression-like behaviors. Eur Neuropsychopharmacol. 2019 Dec;29(12):1419-1432. doi: 10.1016/j.euroneuro.2019.10.012. Epub 2019 Nov 22. PMID: 31767519.
In vitro protocol:
1. Kobayashi T, Hirai H, Iino M, Fuse I, Mitsumura K, Washiyama K, Kasai S, Ikeda K. Inhibitory effects of the antiepileptic drug ethosuximide on G protein-activated inwardly rectifying K+ channels. Neuropharmacology. 2009 Feb;56(2):499-506. doi: 10.1016/j.neuropharm.2008.10.003. Epub 2008 Oct 17. PMID: 18977371.
In vivo protocol:
1. Gadotti VM, Zamponi GW. Ethosuximide inhibits acute histamine- and chloroquine-induced scratching behavior in mice. Mol Brain. 2021 Mar 2;14(1):46. doi: 10.1186/s13041-021-00762-1. PMID: 33653383; PMCID: PMC7927410.
2. Kerckhove N, Boudieu L, Ourties G, Bourdier J, Daulhac L, Eschalier A, Mallet C. Ethosuximide improves chronic pain-induced anxiety- and depression-like behaviors. Eur Neuropsychopharmacol. 2019 Dec;29(12):1419-1432. doi: 10.1016/j.euroneuro.2019.10.012. Epub 2019 Nov 22. PMID: 31767519.
1: Gören MZ, Onat F. Ethosuximide: from bench to bedside. CNS Drug Rev. 2007 Summer;13(2):224-39. Review. PubMed PMID: 17627674.
2: Posner EB, Mohamed K, Marson AG. Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD003032. Review. PubMed PMID: 16235312.
3: Posner EB, Mohamed K, Marson AG. A systematic review of treatment of typical absence seizures in children and adolescents with ethosuximide, sodium valproate or lamotrigine. Seizure. 2005 Mar;14(2):117-22. Review. PubMed PMID: 15694565.
4: Posner EB, Mohamed K, Marson AG. Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents. Cochrane Database Syst Rev. 2003;(3):CD003032. Review. Update in: Cochrane Database Syst Rev. 2005;(4):CD003032. PubMed PMID: 12917940.
5: Wallace SJ. Myoclonus and epilepsy in childhood: a review of treatment with valproate, ethosuximide, lamotrigine and zonisamide. Epilepsy Res. 1998 Jan;29(2):147-54. Review. PubMed PMID: 9477147.
6: Battino D, Estienne M, Avanzini G. Clinical pharmacokinetics of antiepileptic drugs in paediatric patients. Part I: Phenobarbital, primidone, valproic acid, ethosuximide and mesuximide. Clin Pharmacokinet. 1995 Oct;29(4):257-86. Review. PubMed PMID: 8549027.
7: Ichiba M, Kitazawa S. [Ethosuximide]. Nihon Rinsho. 1995 Feb;53 Su Pt 1:915-7. Review. Japanese. PubMed PMID: 8753586.
8: Massey GV, Dunn NL, Heckel JL, Myer EC, Russell EC. Aplastic anemia following therapy for absence seizures with ethosuximide. Pediatr Neurol. 1994 Jul;11(1):59-61. Review. PubMed PMID: 7986296.
9: Millership JS, Mifsud J, Collier PS. The metabolism of ethosuximide. Eur J Drug Metab Pharmacokinet. 1993 Oct-Dec;18(4):349-53. Review. PubMed PMID: 8020533.
10: Wallace SJ. Use of ethosuximide and valproate in the treatment of epilepsy. Neurol Clin. 1986 Aug;4(3):601-16. Review. PubMed PMID: 3092003.
