Succinimide anticonvulsants

Of the succinimide anticonvulsants, ethosuximide is particularly effective in the control of absence seizures. The main side effects of this drug are singultus (hiccups) and sedation at high doses. Hallucinations have also been reputed to occur. Ethosuximide has no beneficial effect in generalized... 

Succinimide Anticonvulsants in Serum Macro- and Micro-Scale Methods Clin. Chem. (Winston-Salem, N. C.) 22 (3) 341-345 (1976) CA 84 173494b... 

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). 

Succinimides — see also Pyrrolidine-2,5-diones as anticonvulsants, I, 166 synthesis, 4, 120 Succinimides, N-hydroxy-polymerization, I, 271-272 Sudoxicam... 

Formal oxidation of pyrrolidine to the succinimide stage affords a series of compounds used as anticonvulsant agents for treatment of seizures in petit mal epilepsy. Knoevnagel condensation of benzaldehyde with ethyl cyanoacetate affords the unsaturated ester, 9. Conjugate addition of cyanide ion leads to the di-nitrile ester (10). Hydrolysis in mineral acid affords the succinic acid (11), presumably by decarboxylation of the intermediate tricarboxyllie acid. Lactamization with methylamine gives phensuximide (12). ... 

As we have seen previously, succinimides containing a quaternary carbon form the basis for a series of anticonvulsant drugs. In the course of research in this series, it was found that the inclusion of additional hetero atoms in the ring was quite compatible with anticonvulsive activity. We consider here the oxa-zolidinediones a discussion of the hydantoins is found later in this section. 

Pregnancy Category C drug and is used with caution during pregnancy. As with all anticonvulsants, when the succinimides are used with other CNS depressants (eg, alcohol, narcotic analgesics, and antidepressants), an additive CNS depressant effect may occur. 

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)... 

Seizure disorder Alone or as an adjunct in the treatment of the Lennox-Gastaut syndrome (petit mal variant), akinetic, and myoclonic seizures. May be useful in patients with absence seizures (petit mal) who have failed to respond to succinimides (see Anticonvulsant section). 

Whether there is any other connection between anticonvulsant activity and camosine s antiaging actions is obviously highly speculative. It may be relevant to note that epileptic seizures and a shortened life span, together with altered protein accumulation, are consequences of PIMT-deficiency in mice, while treatment with valproic acid, an anticonvulsant, partially suppresses these symptoms including effects on life span (Yamamoto et ah, 1998). Conversely, PIMT overexpression can increase life span of Drosophila (Bennet et ah, 2003). Furthermore, the chemistry of some anticonvulsants (ethosuximide) resembles quite closely the structure of the succinimide intermediate formed during both asparagine deamidation and PIMT-mediated repair of isoaspartate residues. One conjectures whether there are any relationships between these... 

The first report of the preparation of the dialkyl succinimide (29-3) dates back to early in the twentieth cenmry. It is consequently surprising to note that it was introduced as an anticonvulsant, under the name ethosuximide, well after its more recently synthesized congeners. The synthetic route starting from methyl ethyl ketone generally follows that above with the exception of the use of ammonia in the last step. The compound thus differs as well by possessing a somewhat acidic imide proton [30]. 

Dni used for the management of convulsive disorders are called anticonvulsants. Most anticonvulsants have specific uses, tliat is, tliey are of value only in the treatment of certain types of seizure disorders. There are five types of dru used as anticonvulsants barbiturates, benzodiazepines, hydantoins, oxazolidinediones, and tlie succinimides. In addition, several miscellaneous dni are used as anticonvulsants. All possess the ability to depress abnonnal neural discharges in tlie central nervous system (CNS), resulting in an inhibition of seizure activity. Dni tliat control generalized tonic-clonic seizures are not effective for absence (petit mal) seizures. If botli conditions are present, combined drug tlierapy is required. 

The various anticonvulsant drugs, containing essentially the meide structure (Table 7.1), belong to the chemical categories of barbiturates, hydantoins, oxazolidinediones and succinimides and lastly the miscellaneous types of compounds possessing such characteristics. 

The following three derivatives of succinimide are anticonvulsants that have found use in the treatment of epilepsy, particularly petit mal seizures. 

Among the many new anticonvulsant succinimides reported, compound XI and related analogs described by Wagner and... 

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