以传统安神中药天麻中微量强镇静催眠有效成分为先导物，经结构优化合成获得新结构化合物YZG-331，有较强镇静催眠活性，已获国家发明专利授权。灌胃给YZG-331有明显的中枢镇静催眠作用，能显著增加非快动眼睡眠但不影响快动眼睡眠、药效持续时间适度、肌松作用轻、降压幅度小，毒性小。YZG-331对腺苷A1和A2A受体亲和力较弱，能明显增加小鼠脑内GABA含量，其镇静催眠作用不能被GABAa受体拮抗剂阻断。拟采用微透析-HPLC-ECD检测YZG-331对动物脑内多种神经递质的影响，阐明其镇静催眠作用的神经化学机制，探究YZG-331引起的单胺类神经递质和腺苷变化与Homer1a蛋白的关系， 以及钙调蛋白激酶通路在其中的作用，并用基因条件性敲除小鼠明确YZG-331镇静催眠作用的靶点。研究结果将为开发新型镇静催眠药提供重要依据。

YZG-331 is an analog of N6-(4-hydroxybenzyl) adenine riboside，which was originally isolated from Gastrodia elata Blume. Our laboratory has previously demonstrated that it can produce strong sedative and hypnotic effects. But its mechanism remains to be determined. The use and structure of YZG-331 has been authorized by the national invention patent. Sleep structure analyses were performed by EEG studies in mice. YZG-331 significantly shortened the latency to NREM sleep, and increased the amount of NREM sleep without changing REM sleep. YZG-331 has week affinity with both adenosine A1 and A2A receptors; also it can increase GABA level in mouse brain. In this program, we intends to further explore the sedative and hypnotic mechanisms of compound YZG-331 through neurotransmitters, CaMKII signaling pathway and protein Homer1a. First ,measure GABA and Glu contents in specific mouse brain regions by HPLC-EC after pre-column derivatization with opthaldialdehyde. Cerebral microdialysis is utilized to determine extracellular GABA and Glu levels. The GABA level is regulated by two enzymes, glutamic acid decarboxylase (GAD) and GABA transaminase (GABA-T). Their activities will be detected if necessary. Calcium/calmodulin-dependent protein kinase II (CaMKII) is an important member of calcium/calmodulin-activated protein kinase family, functioning in sleep-wake regulation. The levels of p-CaMKII, PKA and Synapsin I phosphorylation are quantified via Western blot to explore if CaMKII signal pathway involved in the sedative and hypnotic mechanisms of YZG-331. Homer1a plays an important role of the circle of sleep and wake. The levels of Homer1a are tested by Western blot.And the animals with some genes knocked out are used to determin the receptor of YZG-331.In summary, the aim of this program is to find out the targets and understand the neurochemicahl mechanisms of YZG-331 on sedative and hypnotic effects.