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Ethosuximide

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Chemistry

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Also known as: 77-67-8, Zarontin, Etosuximida, Pyknolepsinum, 2-ethyl-2-methylsuccinimide, Ethosuxide

Molecular Formula

C₇H₁₁NO₂

Molecular Weight

141.17 g/mol

InChI Key

HAPOVYFOVVWLRS-UHFFFAOYSA-N

FDA UNII

5SEH9X1D1D

An anticonvulsant especially useful in the treatment of absence seizures unaccompanied by other types of seizures.

Ethosuximide is an Anti-epileptic Agent. The physiologic effect of ethosuximide is by means of Decreased Central Nervous System Disorganized Electrical Activity.

1 2D Structure

Ethosuximide

2 Identification

2.1 Computed Descriptors

2.1.1 IUPAC Name

3-ethyl-3-methylpyrrolidine-2,5-dione

2.1.2 InChI

InChI=1S/C7H11NO2/c1-3-7(2)4-5(9)8-6(7)10/h3-4H2,1-2H3,(H,8,9,10)

2.1.3 InChI Key

HAPOVYFOVVWLRS-UHFFFAOYSA-N

2.1.4 Canonical SMILES

CCC1(CC(=O)NC1=O)C

2.2 Other Identifiers

2.2.1 UNII

5SEH9X1D1D

2.3 Synonyms

2.3.1 MeSH Synonyms

1. Emeside

2. Ethosuccimid

3. Ethylmethylsuccimide

4. Ethymal

5. Etosuximida Faes

6. Faes, Etosuximida

7. Petnidan

8. Pyknolepsinum

9. Suksilep

10. Suxilep

11. Zarontin

2.3.2 Depositor-Supplied Synonyms

1. 77-67-8

2. Zarontin

3. Etosuximida

4. Pyknolepsinum

5. 2-ethyl-2-methylsuccinimide

6. Ethosuxide

7. 3-ethyl-3-methylpyrrolidine-2,5-dione

8. Ethosuccimide

9. Ethosuccinimide

10. Etosuximid

11. Petnidan

12. Suxinutin

13. Atysmal

14. Emeside

15. Ethymal

16. Suxilep

17. Pentinimid

18. Peptinimid

19. Petinimid

20. Succimitin

21. Zaraondan

22. Capitus

23. Mesentol

24. Pemalin

25. Simatin

26. Succimal

27. Suximal

28. Thetamid

29. Zarodan

30. Zarondan

31. Zartalin

32. Asamid

33. Etomal

34. Pemal

35. Ronton

36. Suxin

37. Aethosuximide

38. Piknolepsin

39. Thilopemal

40. Epileo Petit Mal

41. Zarondan-saft

42. Ethosuximidum

43. Simatin(e)

44. 3-ethyl-3-methyl-2,5-pyrrolidinedione

45. 3-methyl-3-ethylsuccinimide

46. 2-methyl-2-ethylsuccinimide

47. Ci-366

48. 2,5-pyrrolidinedione, 3-ethyl-3-methyl-

49. Pm-671

50. Succinimide, 2-ethyl-2-methyl-

51. 3-ethyl-3-methylsuccinimide

52. Cn-10,395

53. Pm 671

54. 3-methyl-3-ethylpyrrolidine-2,5-dione

55. Alpha-ethyl-alpha-methylsuccinimide

56. Alpha-methyl-alpha-ethylsuccinimide

57. Gamma-methyl-gamma-ethyl-succinimide

58. C.i. 366

59. H 940

60. H-490

61. Cl 366

62. Cn-10395

63. (+-)-2-ethyl-2-methylsuccinimide

64. Nsc-64013

65. Gamma-ethyl-gamma-methyl-succinimide

66. 3-ethyl-3-methylpyrroline-2,5-dione

67. Chembl696

68. .alpha.-ethyl-.alpha.-methylsuccinimide

69. 5seh9x1d1d

70. 3-ethyl-3-methyl-pyrrolidine-2,5-dione

71. Chebi:4887

72. Aethosuccimidum

73. Etosuximide

74. Nsc64013

75. (+/-)-2-ethyl-2-methylsuccinimide

76. .gamma.-methyl-.gamma.-ethylsuccinimide

77. Etosuccimide

78. Etosuccimide [dcit]

79. Aethosuximide [german]

80. Dsstox_cid_3019

81. N-ethyl Methylsuccinimide

82. Dsstox_rid_76832

83. Dsstox_gsid_23019

84. Ethosuximidum [inn-latin]

85. Etosuximida [inn-spanish]

86. Pyknole.psi.num

87. Piknole.psi.n

88. Zarontin (tn)

89. Hsdb 1119

90. Sr-01000075863

91. Einecs 201-048-7

92. Ci 366

93. Nsc 64013

94. Unii-5seh9x1d1d

95. Brn 0117054

96. Cas-77-67-8

97. Ncgc00016320-01

98. Prestwick_611

99. Mfcd00072123

100. Ethosuximide [usan:usp:inn:ban:jan]

101. Spectrum_001385

102. Prestwick0_000165

103. Prestwick1_000165

104. Prestwick2_000165

105. Prestwick3_000165

106. Spectrum2_001483

107. Spectrum3_000944

108. Spectrum4_001051

109. Spectrum5_001073

110. Ethosuximide [mi]

111. E0746

112. (.+/-.)-ethosuximide

113. Ethosuximide [inn]

114. Ethosuximide [jan]

115. 2, 3-ethyl-3-methyl-

116. E 7138

117. Ethosuximide [hsdb]

118. Ethosuximide [usan]

119. Ethosuximide [vandf]

120. Nciopen2_000014

121. Lopac0_000532

122. Schembl34212

123. Bspbio_000029

124. Ethosuximide [mart.]

125. Kbiogr_001342

126. Kbioss_001865

127. 5-21-09-00595 (beilstein Handbook Reference)

128. Divk1c_000218

129. Ethosuximide [usp-rs]

130. Ethosuximide [who-dd]

131. Ethosuximide [who-ip]

132. Spectrum1502196

133. 2,5-pyrrolidinedione, 3-ethyl-3-methyl-, (+-)-

134. Spbio_001465

135. Spbio_001950

136. Bpbio1_000033

137. Gtpl7182

138. Wln: T5vmvtj D2 D1

139. Dtxsid7023019

140. Schembl20541518

141. Ethosuximide (jp17/usp/inn)

142. Ethosuximide, Analytical Standard

143. Hms500k20

144. Kbio1_000218

145. Kbio2_001865

146. Kbio2_004433

147. Kbio2_007001

148. Kbio3_002008

149. Ninds_000218

150. Ethosuximide [orange Book]

151. Hms1568b11

152. Hms1921l14

153. Hms2092d20

154. Hms2095b11

155. Hms3261l05

156. Hms3712b11

157. Hms3885d12

158. Pharmakon1600-01502196

159. Ethosuximide [ep Monograph]

160. Hy-b1378

161. Ethosuximide [usp Monograph]

162. Ethosuximide 1.0 Mg/ml In Methanol

163. Tox21_110370

164. Tox21_500532

165. Bdbm50240424

166. Ccg-39217

167. Ethosuximidum [who-ip Latin]

168. Nsc758192

169. S4626

170. Akos005261742

171. Tox21_110370_1

172. Cs-7976

173. Db00593

174. Lp00532

175. Nsc-758192

176. Sdccgsbi-0050515.p004

177. .alpha.-methyl-.alpha.-ethylsuccinimide

178. Idi1_000218

179. Ncgc00015418-02

180. Ncgc00015418-03

181. Ncgc00015418-04

182. Ncgc00015418-05

183. Ncgc00015418-06

184. Ncgc00015418-08

185. Ncgc00015418-09

186. Ncgc00015418-15

187. Ncgc00093923-01

188. Ncgc00093923-02

189. Ncgc00093923-03

190. Ncgc00093923-04

191. Ncgc00261217-01

192. 3-ethyl-3-methyl-2, 5-pyrrolidinedione

193. As-16859

194. Sbi-0050515.p003

195. 2, 5-pyrrolidinedione, 3-ethyl-3-methyl-

196. Ab00052288

197. Eu-0100532

198. Ft-0668060

199. Ft-0668061

200. C07505

201. D00539

202. D70258

203. Ab00052288_04

204. Zarontin3-ethyl-3-methyl-pyrrolidine-2,5-dione

205. Q421567

206. Sr-01000075863-1

207. Sr-01000075863-3

208. Sr-01000075863-5

209. W-109273

210. 3-ethyl-3-methyl-pyrrolidine-2,5-dione(ethosuximide)

211. Brd-a99633051-001-04-7

212. Brd-a99633051-001-05-4

213. 3-ethyl-3-methyl-pyrrolidine-2,5-dione (ethosuximide)

214. Z2379802739

215. 3-ethyl-5-hydroxy-3-methyl-3,4-dihydro-2h-pyrrol-2-one

216. 4-ethyl-5-hydroxy-4-methyl-3,4-dihydro-2h-pyrrol-2-one

217. 2,5-pyrrolidinedione, 3-ethyl-3-methyl-, (+/-)-

218. Ethosuximide, European Pharmacopoeia (ep) Reference Standard

219. Ethosuximide, United States Pharmacopeia (usp) Reference Standard

220. Ethosuximide Solution, 1.0 Mg/ml In Methanol, Ampule Of 1 Ml, Certified Reference Material

2.4 Create Date

2005-03-25

3 Chemical and Physical Properties

Molecular Formula	C₇H₁₁NO₂
Molecular Weight	141.17 g/mol
XLogP3	0.4
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	1
Exact Mass	141.078978594 g/mol
Monoisotopic Mass	141.078978594 g/mol
Topological Polar Surface Area	46.2 Å²
Heavy Atom Count	10
Formal Charge	0
Complexity	188
Isotope Atom Count	0
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	1
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Covalently Bonded Unit Count	1

4 Drug and Medication Information

4.1 Drug Information

1 of 4
Drug Name	Ethosuximide
PubMed Health	Ethosuximide (By mouth)
Drug Classes	Anticonvulsant
Drug Label	Ethosuximide is an anticonvulsant succinimide, chemically designated as alpha-ethyl-alpha-methyl-succinimide, with the following structural formula:Each ethosuximide capsule contains 250 mg ethosuximide, USP. Also contains: polyethylene glycol 400, N...
Active Ingredient	Ethosuximide
Dosage Form	Syrup; Capsule
Route	Oral
Strength	250mg; 250mg/5ml
Market Status	Prescription
Company	Teva Pharms; Versapharm; Pharm Assoc; Zydus Pharms Usa; Banner Pharmacaps; Mikart

2 of 4
Drug Name	Zarontin
PubMed Health	Ethosuximide (By mouth)
Drug Classes	Anticonvulsant
Drug Label	Zarontin (ethosuximide) is an anticonvulsant succinimide, chemically designated as alpha-ethyl-alpha-methyl-succinimide, with the following structural formula:Each Zarontin capsule contains 250 mg ethosuximide, USP. Also contains: polyethylene glycol...
Active Ingredient	Ethosuximide
Dosage Form	Syrup; Capsule
Route	Oral
Strength	250mg; 250mg/5ml
Market Status	Prescription
Company	Parke Davis

3 of 4
Drug Name	Ethosuximide
PubMed Health	Ethosuximide (By mouth)
Drug Classes	Anticonvulsant
Drug Label	Ethosuximide is an anticonvulsant succinimide, chemically designated as alpha-ethyl-alpha-methyl-succinimide, with the following structural formula:Each ethosuximide capsule contains 250 mg ethosuximide, USP. Also contains: polyethylene glycol 400, N...
Active Ingredient	Ethosuximide
Dosage Form	Syrup; Capsule
Route	Oral
Strength	250mg; 250mg/5ml
Market Status	Prescription
Company	Teva Pharms; Versapharm; Pharm Assoc; Zydus Pharms Usa; Banner Pharmacaps; Mikart

4 of 4
Drug Name	Zarontin
PubMed Health	Ethosuximide (By mouth)
Drug Classes	Anticonvulsant
Drug Label	Zarontin (ethosuximide) is an anticonvulsant succinimide, chemically designated as alpha-ethyl-alpha-methyl-succinimide, with the following structural formula:Each Zarontin capsule contains 250 mg ethosuximide, USP. Also contains: polyethylene glycol...
Active Ingredient	Ethosuximide
Dosage Form	Syrup; Capsule
Route	Oral
Strength	250mg; 250mg/5ml
Market Status	Prescription
Company	Parke Davis

4.2 Therapeutic Uses

Anticonvulsants

National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)

Ethosuximide, the drug of choice, and phensuximide are indicated for the control of seizures in absence (petit mal) epilepsy. /Included in US product labeling/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 271

4.3 Drug Warning

Hemodialysis patients concurrently receiving ethosuximide may require a supplemental dose or an altered dosing schedule, based on the conclusion that ethosuximide is dialyzable.

MARBURY TC ET AL; AM J HOSP PHARM 38(NOV) 1757 (1981)

The most common dose-related side effects are gastrointestinal complaints (nausea, vomiting, and anorexia) and CNS effects (drowsiness, lethargy, euphoria, dizziness, headache, and hiccough). Some tolerance to these effects develops. Parkinsonlike symptoms and photophobia also have been reported. Restlessness, agitation, anxiety, aggressiveness, inability to concentrate, and other behavioral effects have occurred primarily in patients with a prior history of psychiatric disturbance.

Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 535

Urticaria and other skin reactions, including Stevens-Johnson syndrome, as well as systemic lupus erythematosus, eosinophilia, leukopenia, thrombocytopenia, pancytopenia, and aplastic anemia also have been attributed to the drug. The leukopenia may be transient, despite continuation of the drug, but several deaths have resulted from bone-marrow depression. Renal or hepatic toxicity has not been reported.

Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 535

The most common adverse effects of ethosuximide are GI symptoms including anorexia and weight loss, vague gastric upset, cramps, abdominal pain, diarrhea, nausea, vomiting, and epigastric distress.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 2218

For more Drug Warnings (Complete) data for ETHOSUXIMIDE (13 total), please visit the HSDB record page.

4.4 Minimum/Potential Fatal Human Dose

Estimated fatal dose 5 g /From table/

Dreisbach, R. H. Handbook of Poisoning. 9th ed. Los Altos, California: Lange Medical Publications, 1977., p. 311

4.5 Drug Indication

For the treatment of petit mal epilepsy.

FDA Label

Treatment of childhood absence epilepsy

5 Pharmacology and Biochemistry

5.1 Pharmacology

Used in the treatment of epilepsy. Ethosuximide suppresses the paroxysmal three cycle per second spike and wave activity associated with lapses of consciousness which is common in absence (petit mal) seizures. The frequency of epileptiform attacks is reduced, apparently by depression of the motor cortex and elevation of the threshold of the central nervous system to convulsive stimuli.

5.2 MeSH Pharmacological Classification

Anticonvulsants

Drugs used to prevent SEIZURES or reduce their severity. (See all compounds classified as Anticonvulsants.)

5.3 FDA Pharmacological Classification

5.3.1 Active Moiety

ETHOSUXIMIDE

5.3.2 FDA UNII

5SEH9X1D1D

5.3.3 Pharmacological Classes

Decreased Central Nervous System Disorganized Electrical Activity [PE]; Anti-epileptic Agent [EPC]

5.4 ATC Code

N03AD01

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

N - Nervous system

N03 - Antiepileptics

N03A - Antiepileptics

N03AD - Succinimide derivatives

N03AD01 - Ethosuximide

5.5 Absorption, Distribution and Excretion

Absorption

Bioavailability following oral administration is 93%.

Ethosuximide is absorbed from the GI tract. Following oral administration of a single dose, peak blood concentrations are reached within 4 hours; however, about 4-7 days of therapy at usual dosage are required to achieve steady-state plasma concentrations. The plasma concentration required for therapeutic effect is generally considered to range from 40-100 ug/mL; plasma concentrations less than 40 ug/mL are rarely effective. The relationship between plasma ethosuximide concentrations and toxic effects of the drug has not been clearly established; however, plasma concentrations as high as 150 ug/mL have not been associated with signs of toxicity.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 2219

Absorption of ethosuximide appears to be complete, and peak concentrations occur in plasma within about 3 hr after a single oral dose. Ethosuximide is not significantly bound to plasma proteins; during long-term therapy, the concentration in the CSF is similar to that in plasma. The apparent volume of distribution averages 0.7 L/kg.

Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 535

In vitro data suggest that there is no substantial degree of protein binding for ethosuximide. In one study in children, peak CSF concentrations of 25-50 ug/mL were achieved within 1-2 hours following a single 250-mg dose of ethosuximide. These concentrations were maintained for 12-24 hours, and the drug was still detectable in the CSF 65 hours after the drug was given.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 2219

Ethosuximide is excreted slowly in urine. Approximately 20% of a dose is excreted unchanged and up to 50% may be excreted in urine as the hydroxylated metabolite and/or its glucuronide. Small amounts of unchanged drug are also excreted in bile and feces.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 2219

For more Absorption, Distribution and Excretion (Complete) data for ETHOSUXIMIDE (9 total), please visit the HSDB record page.

5.6 Metabolism/Metabolites

Hepatic, via CYP3A4 and CYP2E1.

... Metabolized by hepatic microsomal enzymes.

Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 535

In rats, ethosuximide ... is metabolized into monohydroxyethosuximides, 2-ethyl-3-hydroxy-2-methyl-succinimide ... stereoisomeric 2-(1-hydroxyethyl)-2-methylsuccinimides & ... 2-(2-hydrox yethyl)-2-methylsuccinimide ... which are excreted, in urine, in free form and as ether glucuronides.

The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 262

Different plasma profiles were obtained following admin of ethosuximide...to rat & man... Unchanged drug & only trace amt of metabolites were detected in rat plasma. In human plasma, diastereoisomers of 2-(1-hydroxyethyl)-2-methylsuccinimide...were major components.

The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 552

Ethosuximide is a chiral drug substance primarily indicated for the treatment of absence seizures. This drug is used clinically as the racemate. The human urinary metabolites of ethosuximide (I) have been studied using chiral gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). The metabolites identified were the previously reported unchanged ethosuximide (I) enantiomers, all four stereoisomers of 2-(1-hydroxyethyl)-2-methylsuccinimide (II), and the four stereoisomers of 2-ethyl-3-hydroxy-2-methylsuccinimide (III). Through chemical derivatization methodology and GC/MS two enantiomers of a previously unreported metabolite of ethosuximide, 2-ethyl-2-hydroxymethylsuccinimide (VI), have been identified.

PMID:15931663 Millership JS et al; Biopharm Drug Dispos 26 (6): 225-32 (2005)

5.7 Biological Half-Life

53 hours

A total of 10 epileptic mothers treated with ethosuximide (ES) as well as their 13 newborns were included in this study. At birth fetal/maternal serum concentration ratios were 0.97 +/- 0.02 (n = 7) and ES half-lives in three neonates were 32, 37 and 38 hr. ...

PMID:6508976 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1463560 Kuhnz W et al; Br J Clin Pharmacol 18 (5): 671-7 (1984)

The plasma half-life of ethosuximide is about 60 hours in adults and about 30 hours in children.

McEvoy, G.K. (ed.). American Hospital Formulary Service. AHFS Drug Information. American Society of Health-System Pharmacists, Bethesda, MD. 2007., p. 2219

PMID:6508976 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1463560 Kuhnz W et al; Br J Clin Pharmacol 18 (5): 671-7 (1984)

5.8 Mechanism of Action

Binds to T-type voltage sensitive calcium channels. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channels is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.

Succinimide anticonvulsants are thought to increase the seizure threshold and suppress the paroxysmal three-cycle-per-second spike-and-wave pattern seen with absence (petit mal) seizures. The frequency of attacks is reduced by depression of nerve transmission in the motor cortex. These effects may be due to direct modification of membrane function in excitable cells and/or alteration of chemically mediated neurotransmission. The specific effect of ethosuximide against absence seizures appears to be due to its ability to block T-type calcium channels at concentrations that do not affect other ion channels. /Succinimide Anticonvulsants/

Thomson/Micromedex. Drug Information for the Health Care Professional. Volume 1, Greenwood Village, CO. 2007., p. 271

Ethosuximide reduces low threshold Ca(2+) currents (T currents) in thalamic neurons. The thalamus plays an important role in generation of 3 Hz spike-wave rhythms typical of absence seizures. Neurons in the thalamus exhibit a large amplitude T current spike that underlies bursts of action potentials and likely plays an important role in thalamic oscillatory activity such as 3 Hz spike-wave activity. At clinically relevant concentrations, ethosuximide inhibits the T current, as evident in voltage-clamp recordings in acutely isolated, ventrobasal thalamic neurons from rats and guinea pigs. Ethosuximide reduces this current without modifying the voltage dependence of steady-state inactivation or the time course of recovery from inactivation. By contrast, succinimide derivatives with convulsant properties do not inhibit this current. Ethosuximide does not inhibit sustained repetitive firing or enhance GABA responses at clinically relevant concentrations. Current data are consistent with the idea that inhibition of T currents is the mechanism by which ethosuximide inhibits absence seizures.

Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill, 2001., p. 535

Ethosuximide is an alternative medicament that is used for coupling of petit mal, especially in childhood. Some clinical observations show that it has secondary effects on the gastro intestinal tract (GIT). The present research tries to define the characteristics of Ethosuximide--the inducted secondary effects on the GIT, and to explain some of the possible mechanisms that cause them. The changes that occur in the GIT of patients cured with Ethosuximide are registered roentgenologically. The main change is the atony of the stomach and intestines and the reduced peristaltic activity. The influence of Ethosuximide is examined on smooth muscular samples of human stomach, taken in vitro using stomach resection. The medicament authoritatively reduce the spontaneous bioelectrical activity of the smooth muscular tissue, influences mainly it's components that have Ca+ nature. Together with that is indicated relaxation of the smooth muscular samples. In that research is expressed the thesis that this Ethosuximide reduction of the Ca(+)-influx in the smooth muscular cells and the related relaxation probably are one of the main reasons of the secondary effects on the GIT.

PMID:10205989 Zagorchev P et al; Folia Med (Plovdiv) 40 (3B Suppl 3): 28-33 (1998)

Ethosuximide is one of the means of treatment of minor epilepsy but hardly any data on its mechanism of action are available in the literature. Anticonvulsant agents are known to bring about changes in the functions and in the interaction between some of the mediator systems within the central nervous system. An assessment of the status of neuromediator systems can be made on the basis of the response of isolated smooth muscle strips to the action of agonists and antagonists of various receptors. It was found by the pharmacological analysis of isolated strips from the rat stomach (antrum and corpus strips), the seminal duct and the cervical vein that ethosuximide induces a reduction in the physical contractile activity and the tone of smooth muscle preparations. Smooth muscle relaxation caused by ethosuximide is not blocked by different receptor inhibitors such as dihydroergotamine, propranolol, atropine, chlorpromazine, haloperidol and indomethacin. Ethosuximide causes a significant reduction in the physical contraction of smooth muscles produced by potassium chloride depolarization, with a stronger impact on the subsequent tonic contraction caused by calcium ions. A reduction in the potassium content of the solution has no effect on the nature of the action of ethosutimide. It is thus assumed that the probable mechanism of action of ethosuximide consists in lowering calcium transport since the inhibitors of calcium transport sodium nitroprusside and verapamil intensify the blocking effect of ethosuximide on smooth muscle contractile activity.

PMID:1860492 Toreva D et al; Farmakol Toksikol 54 (1): 23-7 (1991)

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