Intense epileptic seizures are accompanied by an extracellular increase of K+ and decrease of Ca++. Under this circumstance, the synaptic transmission must have been blocked and the seizure is sustained by non-synaptic mechanisms. Therefore, the searching of anti-epileptic drugs acting on non-synaptic targets is being considered as a powerful strategy to control seizures that nowadays are refractory to the available drugs. There is increasing evidence that integrins may participate in epileptogenesis and, therefore, may be considered a non-synaptic target. In the present work we investigate the effect of leucurogin (Leuc), a recently identified disintegrin, on the non-synaptic epileptiform activity (NEA) induced in the dentate gyrus (DG) of a rat (Wistar, male, 100-120g, n = 8) hippocampal slices. The NEA was induced by bathing slices with high-K+ and low-Ca++. The extracellular potential (EP) and intrinsic optical signal (IOS) were used to record the epileptiform events. EPs were quantified according to the parameters: DC-shift (DC), event duration (ED) and population spikes amplitude (PS). Twenty minutes after NEA induction, slices were bathed with solutions containing Leuc. EP recordings performed at the granule cell layer of DG show that with the dosage ~ 33μg/ml of Leuc the NEAs were suppressed. Comparison between the electrographic parameters before and after Leuc application shows non-significant differences. Values are means ± S.E.M. (DC – before: 7.80±0.68 mV, after: 7.57±0.67 mV; ED – before: 35.82±2.35 s, after: 37.63±3.14 s; PS – before: 0.43±0.04 mV, after: 0.38±0.05 mV; n = 40; compared by paired t-test; p<0.05). The IOS shows that during the blockage the entire layer had no NEA. Our data show that Leuc is a potential non-synaptic anti-epileptic drug, which is reversibly recovered after washout. Future work must be addressed to unravel the mechanism responsible for the anti-epileptic effect of Leuc. This perspective may open new avenues on the seizure control.