Platform Development for New Anti-epileptic Drug Evaluation and Pre-clinical Study of New Cholecystokinin Antagonists as New Anti-epileptic Drugs

Epilepsy is a chronic central nervous system disorder. Patients with epilepsy may suddenly lose consciousness and involuntarily convulsion without warning. There are more than 9 million epilepsy patients in China, and one in four patients cannot reduce the frequency of attacks by taking existing drugs. The program aims to understand the pathogenesis of temporal lobe epilepsy and develop new anti-epileptic drugs. Cholecystokinin (CCK) is one of the most abundant neuropeptides in the mammalian nervous system. Our early studies found that CCK is the key to excitatory and inhibitory regulation of the central nervous system, and epilepsy is associated with imbalanced regulation of brain excitation and inhibition. Our recent pilot studies showed that CCK B receptor antagonists can reduce the frequency of spontaneous seizures in mice model of epilepsy, the results were validated in further developed mini-pig models of epilepsy. In this study, we will establish an anti-epileptic drug evaluation platform based on animal models and use it for preclinical therapeutic evaluation of CCK antagonists. We will also design and synthesize new CCK receptor antagonists. For the leading new chemical entities, we will conduct synthetic processes, crystal forms, pharmacokinetic studies, and explore joint drug regimens to further improve intellectual property protection.