腺苷衍生物差向异构体YZG-330和YZG-331的中枢抑制作用比较研究

摘要

Aim To investigate the inhibitory effects of the novel compounds YZG-330 and YZG-331 in central nervous system. Methods The sedative effect was investigated by recording the spontaneous locomotor ac-tivity in mice. The hypnotic effect was evaluated by the latency and duration of the loss of righting reflex ( LORR) in the threshold dosage of sodium pentobarbi-tal treated mice. The two compounds induced the mice that had woken up after a threshold dosage pentobarbi-tal sodium to fall asleep again. The levels of GABA and Glu in brain were measured by HPLC-ECD. Re-sults The results showed that spontaneous locomotor activities decreased in YZG-330 (0.125, 0.5,2 mg·kg-1 ) treated mice and YZG-331 (1.25, 5, 20 mg· kg-1 ) treated mice. YZGs could extend the duration of the loss of righting reflex in threshold dosage of sodium pentobarbital treated mice, and significantly shorten sleep latency. YZGs were able to allow the mice that had woken up after a threshold dosage pentobarbital so-dium to fall asleep again. YZG-331 (40 mg·kg-1 ,i. g. ) could significantly increase GABA level in hypo-thalamus and cerebral cortex. The content of GABA had no significant change after YZG-330 ( 2 mg · kg-1 , ig. ) administration. Conclusions YZG-330 and YZG-331 have potent sedative and hypnotic effects. The efficacy of YZG-330 is stronger than that of YZG-331 , but the mechanism of two compounds sounds different.%目的 研究腺苷衍生物差向异构体YZG-330和YZG-331对小鼠中枢神经系统的抑制作用,并探讨其对小鼠脑内γ-氨基丁酸(GABA)和谷氨酸(Glu)水平的影响.方法 采用开场实验测定小鼠自主活动,以翻正反射消失和恢复的时间作为受试物催眠作用的评价指标;应用OPA柱前衍生化后高效液相色谱-电化学检测法测定小鼠下丘脑及大脑皮层内GABA和Glu含量.结果 差向异构体YZG-330(0.125、0.5、2 mg·kg-1)和YZG-331(1.25、5、20 mg·kg-1)对小鼠自主活动均有较明显的抑制作用,均能明显延长小鼠的睡眠持续时间,并缩短小鼠的入睡潜伏期;YZG-330对小鼠下丘脑和皮层中GABA和Glu水平无明显影响;YZG-331使小鼠下丘脑和皮层中GABA含量明显升高,对Glu水平无明显影响.结论 YZG-330和YZG-331均有明显的镇静、催眠作用,YZG-330表现出的中枢抑制作用强于YZG-331十倍左右,但二者发挥中枢抑制作用的机制存在一定的差异.