The objective of this study is to examine the effects of the endogenous ligands leptin, ghrelin, and neuropeptide Y (NPY) on seizure generation, the oxidant/antioxidant balance, and cytokine levels, which are a result of immune response in a convulsive seizure model. With this goal, Wistar rats were divided into 5 groups Group 1: Saline, Group 2: Saline + PTZ (65 mg/kg), Group 3: leptin (4 mg/kg) + PTZ, Group 4: ghrelin (80 mu g/kg) + PTZ, and Group 5: NPY (60 mu g/kg) + PTZ. All injections were delivered intraperitoneally, and simultaneous electroencephalography (EEG) records were obtained. Seizure activity was scored by observing seizure behavior, and the onset time, latency, and seizure duration were determined according to the EEG records. At the end of the experiments, blood samples were obtained in all groups to assess the serum TNF-alpha, IL-1 beta, IL-6, FGF-2, galanin, nitric oxide (NO), malondialdehyde (MDA), and glutathione (GSH) levels. The electrophysiological and biochemical findings (p < 0.05) of this study show that all three peptides have anticonvulsant effects in the pentylenetetrazol (PTZ)-induced generalized tonic-clonic convulsive seizure model. The reduction of the levels of the pro-inflammatory cytoldnes TNF-alpha, IL-1 beta, and IL-6 caused by leptin, ghrelin, and NPY shows that these peptides may have anti-inflammatory effects in epileptic seizures. Also, leptin significantly increases the serum levels of the endogenous anticonvulsive agent galanin. The fact that each one'of these endogenous peptides reduces the levels of MDA and increases the serum levels of GSH leads to the belief that they may have protective effects against oxidative damage that is thought to play a role in the pathogenesis of epilepsy. Our study contributes to the clarification of the role of these peptides in the brain in seizure-induced oxidative stress and immune system physiology and also presents new approaches to the etiology and treatment of tendency to epileptic seizures. (C) 2016 Elsevier Ltd. All rights reserved.