Methsuximide

Succinimides. Ethosuximide [77-67-8] C2H22NO2 (41) and the related succinknide, methsuximide [77-41-8] C22H23NO2 (42) are used in absence seizure treatment. Like the other anticonvulsants discussed, the mechanism of action of the succinirnides is unclear. Effects on T-type calcium channels and -ATPase activity have been reported (20). Ethosuximide has significant CNS and gastrointestinal (GI) side effect HabiUties (13). 

Methotrimeprazine as analgesic, 1, 168 Methoxalen applications, 4, 707 Methsuximide as anticonvulsant, 1, 166 Methyclothi azide as diuretic, 1, 174... 

The analysis of methsuximide (I) is performed in carbon tetrachloride and of phensuximide (II) in 10% v/v dichloromethane in carbon tetrachloride. In this particular analysis hexamethylcyclotrisiloxane (III) is employed as an internal standard for (I) and (II) whereas the frequencies are referenced to usual tetra-methylsilane (TNS). 

The parent drug phensuximide (4.188) was not enzymatically cleaved, suggesting that Af-alkylation abolishes enzymatic ring opening. Furthermore, no ring-opened metabolites of methsuximide (4.189) were detected. In this case, however, disubstitution of C(2) rather than Afalkylation prevented hydrolysis, since 2-methyl-2-phenylsuccinimide (4.190), its TV-demethylated metabolite, was not a substrate of DHPase [119]. 

Use of acetophenone rather than benzaldehyde in the Knoevnagel condensation reaction affords the unsaturated ester, 13. Elaboration of this to the succinimide by a scheme analogous to that above leads to the anticonvulsant agent methsuximide (14)... 

Methsuximide Absence nd Liver < 1 % excreted unchanged in urine... 

Pharmacokinetics Rapidly metabolized in liver to active metabolite, N-desmethyb methsuximide. Primarily excreted in urine. Unknown if removed by hemodialysis. Half-life 1.4 hr. 

Ethosuximide is the last antiseizure drug to be marketed whose origin is in the cyclic ureide structure. The three antiseizure succinimides marketed in the USA are ethosuximide, phensuximide, and methsuximide. Methsuximide and phensuximide have phenyl substituents, whereas ethosuximide is 2-ethyl-2-methylsuccinimide. 

Phensuximide and methsuximide are phenylsuccinimides that were developed and marketed before ethosuximide. They are used primarily as antiabsence drugs. Methsuximide is generally considered more toxic, and phensuximide less effective, than ethosuximide. Unlike ethosuximide, these two compounds have some activity against maximal electroshock seizures, and methsuximide has been used for partial seizures by some investigators. 

Succinimides Ethosuximide (Zarontin) Methsuximide (Celontin) Affect calcium channels appear to inhibit spontaneous firing in thalamic neurons by limiting calcium entry... 

Drugs in this category include ethosuximide (Zaron-tin), methsuximide (Celontin), and phensuximide (Milontin). All three drugs are primary agents in the treatment of absence (petit mal) seizures, but ethosuximide is the most commonly prescribed. 

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