癫痫合并抑郁症药物分子的设计、合成及药理活性研究

癫痫和抑郁是两个严重威胁人类生命健康的常见疾病。研究发现癫痫与抑郁症的发病具有伴生现象，癫痫患者中同时患有抑郁症的比例高达50%。癫痫合并抑郁患者的治疗要比单纯性癫痫或者抑郁复杂的多，因为给这类患者服用现有的抗癫痫和抗抑郁药都可能会加剧疾病，并提高患者的自杀倾向。因此，研究开发安全的癫痫合并抑郁症药物具有十分重要的意义。前期研究中，我们设计的一类喹啉并三唑衍生物同时表现出抗癫痫和抗抑郁活性。该系列化合物能够对抗最大电惊厥诱导的小鼠惊厥，并显著缩短小鼠强迫游泳实验中的不动时间。本课题拟以该结构母核为先导，对其进行结构优化，通过合成目标化合物并评价其抗癫痫和抗抑郁活性，从中寻找活性高而神经毒性小的化合物。然后对这些化合物进行癫痫合并抑郁模型筛选和作用机制研究，期望可以获得理想的癫痫合并抑郁症候选药物，从而为癫痫合并抑郁症治疗的新药开发奠定基础。

Epilepsy and depression are two of the common diseases seriously threatening life and health of human. The survey indicates that the two conditions coexist in a significant number of patients， the prevalence of depression in people with epilepsy reaches 50%. The cure for epilepsy & depression comorbid is far more complex than that of epilepsy or depression. No matter prescribing antidepressants or anticonvulsants to this specialised group, their illness will be exacerbated and the patients’ suicide will be increased. Therefore, searching for safer drugs for comorbid epilepsy and depression is very significant. In the previous studies, we found that a series of triazole-containing quinolinones exhibited anticonvulsant and antidepressive activities simultaneously. Most of them significantly reduced the immobility time in forced swimming test and inhibited the seizure induced by MES in mice. Based on the above point, in this project, large number of derivatives are designed using this nucleus as the lead. These compounds will be synthesized, and their anticonvulsant and antidepressive activities will be evaluated. Finally, some promising compounds with high activity and low neurotoxicity will be subjected to the screening of epilepsy & depression comorbidity models and research of action mechanism. By completing the project, several candidates will be obtained for the next study, which could pave the way for the development of new agents for the epilepsy & depression comorbidity.