Effects of agomelatine on electrocorticogram activity on penicillin-induced seizure model of rats.

Agomelatine is a new antidepressant drug acting as an antagonist of 5-hydroxytryptamine receptor 2C (5-HTR2C) and agonist of melatonergic receptors 1 and 2 (MT1 and MT2). Because of this dual action, it is an atypical antidepressant. The aim of this study was to investigate chronic anticonvulsant effects of agomelatine on penicillin-induced epilepsy model. Adult male Sprague-Dawley rats divided into four groups and were administered with tap water (vehicle), and agomelatine doses of 10 mg/kg, 50 mg/kg and 100 mg/kg for 14 days via oral gavage. After the last doses were given, epileptic seizures were induced by intracortical penicillin (500 IU/2.5 µl) application in rats under urethane (1.25 g/kg intraperitoneal) anesthesia. Electrocorticogram (ECoG) recordings were obtained from the somatomotor cortex through 90 min, and spike frequencies and amplitudes were analyzed. The spike frequency analyses revealed that only 50 mg/kg agomelatine administration decreased the spike frequencies of hypersynchronous discharge of neurons caused by penicillin (p < 0.05). No significant differences in amplitudes between experimental groups were observed. In addition, mRNA expressions of vesicular glutamate transporter 1 (VGLUT1) and vesicular gamma-aminobutyric acid transporter (VGAT) in response to the agomelatine active dose, 50 mg/kg, showed no significant effect of agomelatine on the mRNA expression. Our results indicate that chronic treatment with agomelatine may have potential anticonvulsant effects. Agomelatine may be a promising drug for epilepsy patients having depression due to its antiepileptic and antidepressant effects.

Anticonvulsant activity of resveratrol-loaded liposomes in vivo.

Resveratrol (3,5,4'-stilbenetriol), a natural polyphenol produced by various plants, has attracted attention over the past decade because of its multiple beneficial properties, including anti-inflammatory, anti-oxidant and chemopreventive, yet, there is limited information about its antiepileptic effects. Moreover, its poor solubility in water and low bioavailability are the challenging issues. In the present study, we aimed to investigate effects of free resveratrol and resveratrol delivered in amphipathic liposomal delivery system, which has a high blood-brain barrier crossing potential, on penicillin-induced epileptic seizure model. For this purpose, adult male Sprague-Dawley rats were divided into four groups as saline (Control), liposome (LIP), free resveratrol (RES) and resveratrol+liposome (RES+LIP). Penicillin-induced epileptic activity was recorded for 120 min by electrocorticography. Glutathione S-transferase (GST), Glutathione (GSH), Superoxide dismutase (SOD) and Malondialdehyde (MDA) assays were performed in brain tissues collected. Our results showed that RES+LIP was the most effective anticonvulsant treatment on penicillin-induced epileptic seizures when compared to control, as RES+LIP immediately decreased the number of spikes per minute. GST and SOD activity, as well as the GSH levels, were significantly increased in the RES+LIP group as compared with the control group. Also, the MDA levels were significantly higher in the RES+LIP compared to RES and control groups. In conclusion, RES+LIP treatment was more effective on the decrease in spike frequency and spike amplitudes than other treatments. Our results suggest that the RES+LIP is more effective than RES on penicillin-induced epileptiform activity.