Better
pharmacotherapies for
epilepsy are needed for patients who are refractory to or have tolerability difficulties with current treatments.
Seletracetam, a new
drug in
epilepsy development, is a
pyrrolidone derivative structurally related to
levetiracetam (trade name
Keppra). It was discovered because of its high binding affinity to the synaptic vesicle 2A (SV2A)
protein, which is now known to be the binding site for this family of compounds.
Seletracetam shows very potent seizure suppression in models of acquired or genetic
epilepsy, as well as high CNS tolerability in various animal models. Pharmacokinetic studies in animals suggest that
seletracetam is rapidly and highly absorbed, with linear and time-independent pharmacokinetics.
Seletracetam appears neither to inhibit nor to induce the major human
drug metabolizing
enzymes, and it demonstrates low
plasma protein binding (<10%), which suggests a low potential for
drug-drug interactions. Initial studies in humans demonstrated first-order monocompartmental kinetics with a half-life of 8 h and an oral bioavailability of >90%. Studies in healthy volunteers showed that the treatment emergent adverse events were of mild to moderate severity, were mostly of CNS origin and were resolved within 24 h. Altogether, these results suggest that
seletracetam represents a promising new
antiepileptic drug candidate, one that demonstrates a potent, broad spectrum of seizure protection and a high CNS tolerability in animal models, with initial clinical findings suggestive of straightforward pharmacokinetics and good tolerability.