Abstracts

Rationale: Blood-brain barrier (BBB) is the most important vascular barrier of the central nervous system (CNS). This protective barrier between blood vessels and brain tissues, allows blood to flow freely to the brain, but prevents contact between the majority of substances from the bloodstream and brain cells. The BBB protects the brain from the effects of many toxic compounds, but also difficult the delivery of drugs to the brain. BBB changes have been observed in brain tissue from people with epilepsy and in experimental models, which could explain their role in the development and progression of epilepsy (epileptogenesis) and the development of drug resistance. The treatment of epilepsy is conditioned by the limited penetration of drugs through the BBB. Models are needed to detect the brain penetration of antiepileptic drugs. BBB in vitro models could be a useful tool to assess the penetration of new therapeutic molecules. Until present, it is not known the passage through the BBB of Lacosamide (LCM). Objective: To determine whether penetration ratio of LCM through BBB is similar to the classic Antiepileptic drugs such as Valproic acid (VPA) and Carbamazepine (CBZ).Methods: In order to determine the ability of compounds to penetrate into CNS we used an　in vitro　model of BBB (RBT-24H, BBB Kit, PharmaCo-Cell Company Ltd. Nagasaki, Japan). This model was reconstructed by the culture of both primary rat brain micro vascular endothelial cells and rat brain pericytes separated by a macro porous Millicell membrane (24 wells, pore size: 3.0μm, Millipore, Bedford, MA, USA). Briefly, we pre-incubated the BBB kits at 37 °C in 5% CO2 for 4–5 days, in order to strongly reconstruct the barrier integrity and tight-junctions.Results: A drug with an apparent permeability coefficient (Papp) above 20 x 10–6 cm/s was considered to have a very good penetration into the CNS, while a　compound with a Papp lower than 10 x 10–6　cm/s was considered a low penetrant　CNS drug. As expected, LCM, VPA and CBZ were found at the brain side with a Papp over 20 x 10–6 cm/s (Fig 1).Conclusions: LCM has a passage through the BBB similar to the classics AEDs such as VPA and CBZ. This new model could help to determine the passage of AED through the BBB.