Mesuximide

Ethosuximide and mesuximide are succinimides. Ethosuximide is the agent of first choice for the management of absence (petit mal) seizures. It inhibits low-threshold Ca" " currents in the thalamus. As it may precipitate grand mal seizures it is frequently given together with a barbiturate or with phenytoin to prevent that. Its plasma concentrations do not closely correlate with the therapeutic effects. 

Figure 19 Enantiomer separation of mesuximide (left) and phen-suximide (right) on a 25-m fused silica capillary with 3-ac-2,6-pe-3 CD at 180°C.

Mesuximide (A,2-dimethyl-2-phenylsuccmimide) is a suc-cinimide anticonvulsant with actions similar to those of ethosuximide. Its activity is mostly due to its main metabolite, A-desmethylmesuximide, which has a half-hfe of about 48 hours (1). 

Of 26 patients with complex partial seizures refractory to phenytoin, carbamazepine, phenobarbital, or primidone, mesuximide produced a 50% or greater reduction in seizure frequency in eight after 8 weeks, and five of those continued to benefit after 3-34 months (1). Drowsiness, gastrointestinal disturbances, hiccups, irritability, and headache were the common adverse effects. 

Mesuximide can cause profound nervous system depression (3). In one patient this responded to charcoal hemo-perfusion (1). 

In a retrospective study, in which 376 samples from 222 patients were analysed, mesuximide induced the metabolism of lamotrigine and reduced lamotrigine concentrations by about 70% (4). 

In 17 patients (12 men, 5 women aged 8-19 years) the mean valproic acid concentration was 82 pg/ml while not taking mesuximide and 56 pg/ml while taking mesuximide (5). In eight patients who stopped taking mesuximide the mean serum concentration increased from 50 pg/ml to 72 pg/ml. 

Sherwin, A. L., Ethosuximide Chnical use, m Antiepileptic Drugs, 4th ed.. Levy, R. H., Mattson, R. H., and Meldrum, B. S., Eds., Raven Press, New York, 1994. Battino, D., Estienne, M., and Avanzini, G., Chnical pharmacokinetics of antiepileptic drugs in paediatric patients. Part 1 Phenobarbital, primidone, valproic acid, ethosuximide and mesuximide, Clin. Pharmacokinet., 29 257-286, 1995. 

Phenobarbital, phenytoin, and possibly felbamate increase the levels of the active metabolite of mesuximide, IV-desmethylmesux-imide. Mesuximide increases the serum levels of phenobarbital and phenytoin, and decreases the levels of lamotrigine, and to a lesser extent, valproate. 

A study in hospitalised patients with petit mal epilepsy found that when mesuximide was given to 8 patients taking phenobarbital and 13 patients taking primidone, the mean serum levels of phenobarbital rose by 38% and 40%, respectively. Dose reductions were needed in 50% and 62% of patients, respectively. It was also found that the concurrent use of phenobarbital increased the serum levels of the active metabolite of mesuximide, A-desmethylmesuximide. ... 

A retrospective analysis of serum valproate levels was carried out in 17 patients who started and/or stopped taking mesuximide and whose concurrent medication remained unaltered. In the 14 patients starting mesuximide, a mean decrease in valproate levels of 32% was seen. In the 8... 

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