Agents Whose Mechanism of Action Is Not Known

Agents Whose Mechanism of Action Is Not Known

Felbamate

Felbamate (Felbatol) was introduced with the expecta-tion that it would become a major drug in the treatment of epilepsy. Felbamate exhibited few manifestations of serious toxicity in early clinical trials. Soon after its in-troduction, however, it became apparent that its use was associated with a high incidence of aplastic anemia. Consequently, felbamate is indicated only for patients whose epilepsy is so severe that the risk of aplastic ane-mia is considered acceptable.

While its mechanism of action has not been clearly established, felbamate shows some activity as an in-hibitor of voltage-dependent sodium channels in a man-ner similar to that of phenytoin and carbamazepine. Felbamate also interacts at the strychnine-insensitive glycine recognition site on the NMDA receptor– ionophore complex. Whether this effect is important to its anticonvulsant activity is not clear.

Gabapentin

Gabapentin (Neurotonin) was initially designed to be a rigid analogue of GABA. When it was discovered to have antiepileptic properties, it was assumed that this activity was related to a GABAergic mechanism. However, subsequent studies have failed to show any GABAergic activity of gabapentin. Although it has not yet been possible to ascribe any definite mechanism to its antiepileptic activity, there is recent evidence that it may function as an agonist at GABA_B receptors in the brain.

Gabapentin is recommended as adjunctive therapy in the treatment of partial seizures in adults. When used with other drugs, it appears to be an effective AED; it is usually not effective when employed alone for patients with severe seizures.

Gabapentin is generally well tolerated, with somno-lence, dizziness, and ataxia the most commonly reported adverse effects. A low incidence of potentially serious side effects and no significant allergic reactions have been reported.

Levetiracetam

Levetiracetam (Keppra) has recently been approved for the treatment of partial-onset seizures. It appears to be safe and effective; its exact therapeutic profile has yet to be determined. It does not appear to share any of the mechanisms of action of agents that have been dis-cussed to this point. It does have a highly specific brain binding site, but the significance of this observation to its mechanism of action has not been elucidated.