Sedative And Hypnotic Activity Of 0605 And Its Mechanism

Objective: 0605 is a compound that was oriented synthe- sized by Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. We have examined the 0605's activity of anti-schizophrenia, anti-mania, anti-anxiety, and found that the sedative and hypnotic activity is significant. Because the compound hasn't been apply for a patent, so the chemical structure is classified.This paper seeks to further clarify the sedative and hypnotic activity of compand 0605, and the mechanism for research.Methods: This paper is divided into three parts, the first part of "The Experimental study of compound 0605 on the behavior" uses the following method to systematic study the sedative and hypnotic effects of compound 0605: the experiment of spontaneous locomotor activity, the experiment of sleep latency and sleep time induced by sodium pentobarbital, the experiment of sleep induced by subthreshold dosage of sodium pentobarbital, the experiment of again sleep induced by sodium pentobarbital.The second part of "The effect of compound 0605 on monoamain neurotransmitters in forebrain of mice" detected the content of NE,DA,5-HT,5-HIAA and DOPAC by HPLC.The third part of "The effect of compound 0605 on mona- main neurotransmitters and the activity of monoamine oxidase B in different parts of brain of rat " choses rats for experiment. Based on the second part, it's further detected the content of monoamine neurotransmitters and the activity of monoamine oxidase B by kit.Results: The first part: 0605 (intraperitoneal injection administration or intragastric administration) can significantly reduce the spontaneous locomotor activity in mice; reduce the sleep latency induced by sodium pentobarbital in mice; extension the sleep time induced by sodium pentobarbital in mice; increase the sleep induced by subthreshold dosage of sodium pentobarbital in mice; increase the again sleep induced by sodium pentobarbital in mice.The second part: Compared with the control group, the content of NE in 0605 Group decreases by 35 percent, a significant difference, P <0.01; the content of DA decreased by 8%, but there was no significant statistical difference; the content of DOPAC increased by 36%, P <0.05; the content of 5-HT and 5-HIAA had no significant change; the ratio of DOPAC/DA increased by 43%, a significant difference, P <0.05.The third part: the effect of 0605 on monoamine neurotransmitter: in the cortex, between the 0605 group and the control group, there is no significant difference for all monoamine neurotransmitters; in the hypothalamus, the content of NE in 0605 Group has decreased 30%, and the ratio of DOPAC/DA increased by 32%, P <0.05; in the striatum, the content of DA in 0605 group decreased by 21%, the ratio of DOPAC/DA increased by 43%, P <0.01; in the hippocampus, the content of 5-HIAA in 0605 group decreased 22%, P <0.01.The effect of compound 0605 on the activity of monoamine oxidase B: Compared with the control group, the activity of monoamine oxidase B in 0605 group increased by 72%, P <0.01.Conclusion: 1 Series of behavioral experiments and biochemical experiments show that: 0605 has obvious sedative and hypnotic effects on the nervous system. 2 With the enhanced monoamine oxidase B activity, 0605 contributed to the NE and DA metabolism, resulted in the decreasing of NE and DA in the brain of rat. 3 We speculate that 0605 played a sedative and hypnotic effect by reducing the content of NE and DA in brain. 4 the sedative and hypnotic effects of 0605 may be related to the impact that 5-HT played on 5-HT receptor.