title: Seletracetam (UCB 44212).
abstract: 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.
authors.affiliation: CNS Clinical Development, UCB Atlanta, Smyrna, Georgia 30080, USA. Barbara.bennett@ucb-group.com
authors.forename: Barbara
authors.initials: B
authors.lastname: Bennett
authors.forename: Alain
authors.initials: A
authors.lastname: Matagne
authors.forename: Philippe
authors.initials: P
authors.lastname: Michel
authors.forename: Michèle
authors.initials: M
authors.lastname: Leonard
authors.forename: Miranda
authors.initials: M
authors.lastname: Cornet
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Meeus
authors.forename: Nathalie
authors.initials: N
authors.lastname: Toublanc
mesh_terms: D000818:Animals; D000927:Anticonvulsants; D001921:Brain / Q000187:drug effects*; D002986:Clinical Trials as Topic; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D011760:Pyrrolidinones / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D011760:Pyrrolidinones; C518915:Seletracetam