Wauquier, A., J. Fransen, W. Melis, D. Ashton, J.-M. Gillardin, P.J. Lewi, G. Van Clemen, J. Vaught, and P.A.J. Janssen: Loreclezole (R 72 063): An anticonvulsant chemically unrelated to prototype antiepileptic drugs. Drug Dev. Res. 19:375-392, 1990. This study reports on the anticonvulsant profile of a chemically and pharmacologically new compound, loreclezole, as compared to prototype antiepileptics. The compound was tested in different species (mice, rats, guinea pigs, and dogs), in different seizure models, following p.0. or i.p. drug administration, and at different time intervals. Loreclezole was found to be active in a genetic model of reflex epilepsy (audiogenic seizures in mice) and in all models where seizures were elicited by chemical or electrical stimulation. In addition, loreclezole was active against both tonic (TON) and clonic (CLON) seizures and increased the threshold for behavioral as well as electroencephalographic (EEG) seizures. Loreclezole has a rapid onset of action (15 min in the quinolinic acid-induced CLON seizures and barrel rotations) and a duration of action, in certain tests, of more than 24 hr (allylglycine test and S.C. pentylenetetrazol test in rats). There is a dissociation between the anticonvulsant doses and the induction of neurological side effects (in dogs, ratio >25.5). Chronic administration for 5-7 days did not lead to tolerance to the anticonvulsant action of loreclezole. Also, as based on spectral map analysis, loreclezole resembles both valproate and ethosuximide, suggesting that it might be effective against both grand ma1 and petit mald epilepsy.
