The Mechanism Study of YZG-331 on Sedative and Hypnotic Effect

YZG-331 is a synthetic novel derivates of N6 -(4-hydroxybenzyl) adenine riboside (NHBA), which has potent sedative and hypnotic effects based on our previous study. We are now aiming to investigate the mechanism of YZG-331. In this research, the behavioral studies showed that YZG-331 could reduce the spontaneous locomotor activity in mice, which can be blocked by non-selective adenosine receptor antagonist AM, adenosine A1 receptor (A1R) antagonist DPCPX and adenosine A2a receptor (A2aR) antagonist SCH58261, respectively. Moreover, YZG-331 no longer exerts sedative effect, when A1R or A2aR was knocked down using adeno-associated virus in mice. YZG-331 prolongs the sleep time in mice treated with pentobarbital sodium, which can be prevented by DPCPX or SCH58261. The above results demonstrate that YZG-331 exerts sedative and hypnotic effects through A1R and A2aR. In addition, it is found that YZG-331 decrease intracellular calcium level and reduce CaMKII phosphorylation (pCaMKII) level of the hypothalamus and cortex in mice. In summary, this study indicates that the sedative and hypnotic effects of YZG-331 may be attributed to the activation of A1R and A2aR and involve the Ca2+ -CaMKII signaling pathway.