Antiseizure drugs structure

The antiseizure drugs exhibit many similar pharmacokinetic properties—even those whose structural and chemical properties are quite diverse— because most have been selected for oral activity and all must enter the central nervous system. Although many of these compounds are only slightly soluble, absorption is usually good, with 80-100% of the dose reaching the circulation. Most antiseizure drugs (other than phenytoin and valproic acid) are not highly bound to plasma proteins. 

Although not obvious from a two-dimensional representation of its structure, carbamazepine has many similarities to phenytoin. The ureide moiety (-N-CO-NH2) in the heterocyclic ring of most antiseizure drugs is also present in carbamazepine. Three-dimensional structural studies indicate that its spatial conformation is similar to that of phenytoin. 

Topiramate is a substituted monosaccharide that is structurally different from all other antiseizure drugs. 

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. 

The oxazolidinediones contain an oxazolidine heterocyclic ring (Figure 24-1) and are similar in structure to other antiseizure drugs introduced before 1960. The structure includes only short-chain alkyl substituents on the heterocyclic ring, with no attached phenyl group. 

Felbamate is a dicarbamate that is structurally similar to the antianxiety drug meprobamate. It was approved by the U.S. FDA for antiseizure use in 1993. Following the occurrence of rare cases of aplastic anemia and of severe hepatotoxicity associated with the use of felbamate during early 1994, however, a black box warning was added to the drug s package insert (53). 

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