Ethosuximide

IUPAC nomenclature

(RS)-3-Ethyl-3-methyl-pyrrolidine-2,5-dione

Classification

Ethosuximide is a succinimide anticonvulsant.

Physiochemical Properties

Mechanism of Action

Ethosuximide binds with T-type voltage sensitive calcium channels. The latter involves in mediating the entry of calcium ions into excitable cells and are also involves in variety of calcium-dependent processes, including muscle contraction, hormone release, neurotransmitter release, gene expression, cell division and cell death.

T-type voltage sensitive calcium channel are also involved in the modulation of firing patterns or neurons which is necessary for the information processing and also in cell growth processes.

Structure Activity Relationship

SAR of succinimides can be discussed as follows:

• Phenyl substitution makes them active against electrically induced convulsion.
• N-methylation decreases activity against electroshock seizures.
• N-methylation also increases the activity against chemically induced convulsions.

Method of synthesis

i. Methylethylketone and cyanoacetic ester are condensed in Knoevanagel reaction conditions.

ii. Hydrogen cyanide is added to the resulting product.

iii. Dinitrile so formed undergoes acidic hydrolysis and decarboxylation to form 2-methyl-2-ethylsucinic acid.

iv. Reaction of the above formed compound with ammonia gives a diazonium salt which on heterocyclization produces ethosuximide.[1]

Therapeutic Uses

Ethosuximide is used for:

• The control and prevention of absence or petit mal seizure

Side Effects

Side effects of Ethosuximide are: 

• Dizziness
• Drowsiness
• Abdominal pain
• Loss of appetite
• Nausea
• Vomiting
• Headache
• Diarrhea
• Weight loss
• Depression
• Suicidal thoughts
• Mood changes
• Signs of infections
• Swollen joints and pain
• Rashes
• Tiredness
• Rapid breathing
• Fainting
• Liver problems

MCQs 

Q.1 Match the following with correct SAR of the drug ethosuximide.

a) i-A, ii-C

b) i-A, ii-D

c) i-B, ii-C

d) i-B, ii-D

Q.2 Correct sequence for the True/False for correct IUPAC names of the drug can be?

• Ethosuximide: [(2R,3S,4S,5R)-5-(6-amino-2-fluoro-purin-9-yl)- 3,4-dihydroxy-oxolan-2-yl]methoxyphosphonic acid
• Cytarabine: 4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5- (hydroxymethyl)oxolan-2-yl] pyrimidin-2-one
• 5-FU: 5-Fluoro-1H,3H-pyrimidine-2,4-dione
• Fludarabine: (RS)-3-Ethyl-3-methyl-pyrrolidine-2,5-dione

a) TTFF

b) FFTF

c) TTFT

d) FTTF

Q.3 Correct statement related with the solubility of the drug ethosuximide from the following is?

a) Practically insoluble in water

b) Sparingly soluble in water

c) Soluble in water

d) Freely soluble in water

Q.4 Ethosuximide binds which type of channels?

a) Sodium channels

b) Potassium channels

c) Voltage sensitive calcium channels

d) Chloride ion channels

Q.5 Which amongst the following is not a therapeutic use of drug Ethosuximide?

a) Treatment of Arrhythmias

b) Treatment of diarrhea

c) Treatment of Goiter

d) All of the above

Q.6 Which of the following drug and their classification are correct?

I. Ethosuximide: Succinimide anticonvulsant drug

II, Sodium salicylate: anti-inflammatory drug

III. Chlordiazepoxide: Phenothiazine antipsychotic drug

IV. Methoxyflurane: Morphine analogue

a) I, II

b) II, IV

c) II, III

d) II, IV 

Q.7 The correct octanol/water partition coefficient of drug ethosuximide is?

a) -3.2

b) 0

c) 0.38

d) 5.4

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ANSWERS

1-b

2-d

3-d

4-c

5-d

6-a

7-c

REFERENCES