NEW ANTICONVULSANT DRUGS - FOCUS ON FLUNARIZINE, FOSPHENYTOIN, MIDAZOLAM AND STIRIPENTOL

In the past decade, several new antiepileptic drugs have been tested. Most recently, 5 new antiepileptic drugs have been launched onto Europ ean and US markets. These include vigabatrin, oxcarbazepine and lamotr igine in Europe, and felbamate and gabapentin in the US, In addition t o these, 3 additional drugs are in the clinical investigational stage: flunarizine, fosphenytoin and stiripentol. A fourth agent is midazola m, which was originally introduced in 1986, but recently has shown eff ectiveness in the treatment of status epilepticus. Flunarizine is a se lective calcium channel blocker that has shown anticonvulsant properti es in both animal and human studies. It is a long-acting anticonvulsan t that clinical studies have shown to have effects similar to those of phenytoin and carbamazepine in the treatment of partial, complex part ial and generalised seizures. Fosphenytoin was developed to eliminate the poor aqueous solubility and irritant properties of intravenous phe nytoin. It is rapidly converted to phenytoin after intravenous or intr amuscular administration. In clinical studies. this prodrug showed min imal evidence of adverse events and no serious cardiovascular or respi ratory adverse reactions. It may have a clear advantage over the prese nt parenteral formulation of phenytoin. Midazolam is a benzodiazepine that is more potent than diazepam as a sedative, muscle relaxant and i n its influence an electroencephalographic measures. It has been shown to he an effective treatment for refractory seizures in status epilep ticus. Stiripentol has anticonvulsant properties as well as the abilit y to inhibit the cytochrome P450 system. There are significant metabol ic drug interactions between stiripentol and phenytoin, carbamazepine and phenobarbital (phenobarbitone). Stiripentol has been studied in pa tients with partial seizures, refractory epilepsy and refractory absen ce seizures with some efficacious results.