The Antiepileptic Pharmacodynamics Reseach Of ZZZ

Objectives: Epilepsy, a chronic encephalopathy characterized by spontaneous recurrent seizures results from a variety of causes.Its pathogenesis has not been totally understood yet. Currently, therapeutic drugs for epilepsy depend on alleviating epileptic seizure by inhibiting epileptiform disch arges of various ion channel and the spread of epileptic wave. Due to efficiency and safety issues, new treatment strategies are urgent. Based on our previous research, ZZZ has potential anti-epileptic effect and may be a promising candidate for epilepsy therapy. This project is to investigate the efficacy of ZZZ on epileptic animal models induced by different chemical reagents. Furthermore, its synergistic effect on epilepsy is determinated by combination regimen. And its benefit on learning and memory for epilepsy animal model is also studied.Methods& Materials: This research involves comprehensive epilepsy animal models. Among them, acute mouse models are induced by penicillin, isoniazid or pentetrazol. Spontaneous chronic model is induced by pilocarpine. Acute seizure rat models for Non-spontaneous chronic epileptic are induced by pentetrazol and pilocarpine, namely "two hits". Totally, 100 SD rats or mices are randomly assigned into 10 groups in penicillin, isoniazid and pentetrazol models,it also similar to other epilepsy animal models. Contrast research are med between and commercially available drugs, including LTG,CBZ,VPA and PHT.Anti-epilepsy synergistic effect is detected by combining ZZZ with low dose of drugs, which are not efficient at the given doses. Relevant indications are collected and analyzed. Seizure incubation period, incidence of epilepsy, epilepsy seizures score, rate of weight loss and rate of death for acute model. While, animals color, behavior and seizures change, and drug withdrawal reaction for chronic model. Learning and memory ability for epilepsy animal are studied by water maze test.Results:ZZZ holds a brand-new antiepileptic mechanism, which regulates astrocyte energy and metabolism. Optimized regimen of ZZZ can prolong the seizure incubation period, reduce the seizure score, and decrease mortality. Other antiepileptic effects have been shown on the acute and chronic epilepsy animal secondary acute induced model. The anti-epileptic effect of ZZZ in chronic epilepsy model is consistent with acute epilepsy model and has no significant withdrawal response. Data indicate ZZZ has anti-epilepsy synergistic effect with different drugs. Results of water maze test demonstrate that ZZZ can promote the epilepsy animal learning and memory ability, rather than deteriorate it. Furthermore, anti-epilepsy synergistic effect of ZZZ can also be founded water maze test.Conclusions: Our research suggests that ZZZ has broad-spectrum anti-epileptic effect and slight adverse effects. It is a promising drug candidate that can be used singly or combining with other drugs to treat epilepsy and prevent complication involved.