METHSUXIMIDE Chemical Properties

Melting point:

52-53°

Boiling point:

bp0.1 121-122°

Density 

1.1255 (rough estimate)

refractive index 

1.5440 (estimate)

storage temp. 

Refrigerator

solubility 

Chloroform (Slightly), Methanol (Slightly)

form 

Solid

color 

White to Off-White

Water Solubility 

2.8g/L(25 ºC)

Safety Information

HS Code 

2925190100

Hazardous Substances Data

77-41-8(Hazardous Substances Data)

Toxicity

LD50 orally in mice: 0.9 g/kg (Marshall, Vallance)

METHSUXIMIDE Usage And Synthesis

Description

Methsuximide is a succinimide that is converted to N-desmethylmethosuximide, a channel blocker that targets low threshold calcium currents. Methsuximide is a substrate of cytochrome P450 (CYP) isoform 2C19 that, in turn, inhibits CYP2C19-mediated metabolism of biguanides. Methsuximide has been shown to have anticonvulsant properties in clinical trials.

Chemical Properties

Light Yellow Oil

Originator

Celontin,Parke Davis,US,1957

Uses

A calcium channel succinimide antiepileptic drug. Anticonvulsant.

Definition

ChEBI: Methsuximide is an organic molecular entity.

Manufacturing Process

100 g of α-phenyl-α-methylsuccinic acid and 110 g of 40% aqueous methyl amine are heated together at 200 to 250°C until no more distillate is obtained. Upon vacuum distillation of the residue, the N-methyl-α-phenyl-αmethylsuccinimide, of BP 121° to 122°C at 0.1 mm is obtained. After recrystallization from aqueous ethanol, this compound melts at 52° to 53°C.

brand name

Celontin (Parke-Davis).

Therapeutic Function

Anticonvulsant

Clinical Use

Although methsuximide is less commonly used, it may be indicated for the control of absence seizures refractory to other drugs. Although it does not precipitate tonic-clonic convulsions, it often is combined with phenytoin or phenobarbital when absence seizures coexist with tonic-clonic symptoms. Much of the efficacy of methsuximide is attributed to its desmethyl metabolite. The half-life of methsuximide is between 2.6 and 4.0 hours, but the half-life for N-desmethylsuximide is 25 hours, causing it to accumulate substantially. Concentrations of greater than 40 g/mL may be associated with toxicity. Methsuximide is considered to be more toxic than ethosuximide.

References

[1] nicholls, p. j., and orton, t.c. the physiological disposition of 14c-methsuximide in the rat. br.j.pharmacol. 45(1), 48-59 (1972).
[2] chen g, weston j k, bratton a c. anticonvulsant activity and toxicity of phensuximide, methsuximide and ethosuximide[j]. epilepsia, 1963, 4(1‐4): 66-76.
[3] sigler m, strassburg h m, boenigk h e. effective and safe but forgotten: methsuximide in intractable epilepsies in childhood[j]. seizure, 2001, 10(2): 120-124.
[4] wright j d, helsby n a, ward s a. the role of s‐mephenytoin hydroxylase (cyp2c19) in the metabolism of the antimalarial biguanides[j]. british journal of clinical pharmacology, 1995, 39(4): 441-444.
[5] guengerich f p. human cytochrome p450 enzymes[m]//cytochrome p450. springer us, 1995: 473-535.

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