Morningness–eveningness and treatment response in major depressive disorder

In a large, prospective, 8-week open study of 721 outpatients receiving agomelatine treatment for a current major depressive episode (MDE), morningness–eveningness (Composite Scale of Morningness) was assessed before and after treatment to investigate possible changes in morningness–eveningness after treatment and evaluate whether morningness–eveningness at baseline predicted treatment response. A change towards morningness was observed after treatment. This change was greater in responders than non-responders. Moreover, being a morning type at baseline was an independent predictor of response to treatment. Once thought to be a trait variable, morningness–eveningness is a potential treatment target that should be systematically assessed in MDE patients.     

舒肝解郁胶囊联合阿戈美拉汀对抑郁症患者血清单胺类神经递质和神经功能相关因子的影响

摘要 目的：观察舒肝解郁胶囊联合阿戈美拉汀治疗抑郁症的疗效及对血清单胺类神经递质和神经功能相关因子的影响。方法：纳入我院2017年5月~2020年5月接诊的120例抑郁症患者,经双色球随机分组法将患者分为对照组和观察组,各为60例。对照组患者予以阿戈美拉汀治疗,观察组患者予以舒肝解郁胶囊联合阿戈美拉汀治疗。比较两组疗效、血清单胺类神经递质、神经功能相关因子、抑郁焦虑评分及不良反应发生率。结果：观察组的临床总有效率为93.33%（56/60）,高于对照组的73.33%（44/60）（P<0.05）。两组治疗6周后汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）评分较治疗前降低,且观察组较对照组低（P<0.05）。两组治疗6周后多巴胺（DA）、去甲肾上腺素（NE）、5-羟色胺（5-HT）水平较治疗前升高,且观察组高于对照组（P<0.05）。两组治疗6周后S100?茁、髓磷脂碱性蛋白（MBP）、神经元特异性烯醇化酶（NSE）水平较治疗前降低,且观察组低于对照组（P<0.05）。两组不良反应发生率对比无差异（P>0.05）。结论：舒肝解郁胶囊联合阿戈美拉汀治疗抑郁症,疗效显著,可有效调节血清单胺类神经递质和神经功能,改善抑郁症状,且安全可靠。     

阿戈美拉汀联合舍曲林治疗抑郁症伴失眠的疗效及对睡眠质量评分、多导睡眠监测参数和血清神经递质的影响

摘要 目的：观察阿戈美拉汀联合舍曲林治疗抑郁症伴失眠的疗效及对睡眠质量评分、多导睡眠（PSG）监测参数和血清神经递质的影响。方法：选取2020年4月~2021年12月期间来贵州省第二人民医院就诊的80例抑郁症伴失眠患者作为观察对象,采用随机数字表法分为实验组和对照组各40例,对照组患者接受舍曲林治疗,实验组患者接受阿戈美拉汀联合舍曲林治疗,对比两组疗效、匹兹堡睡眠质量指数（PQSI）评分、PSG相关指标参数、汉密尔顿抑郁量表（HAMD）评分、血清神经递质水平变化,记录两组治疗期间不良反应发生情况。结果：实验组的临床总有效率为90.00%（36/40）,高于对照组的67.50%（27/40）,差异有统计学意义（P<0.05）。两组治疗8周后PSQI、HAMD评分均下降,且实验组的变化程度大于对照组（P<0.05）。两组治疗8周后睡眠总时间（TST）、睡眠效率（SE）、非快速眼动睡眠阶段3+4的百分比（SWS）、快速眼动睡眠阶段睡眠时间（RT）增加,非快速眼动睡眠阶段1的百分比（S1）、非快速眼动睡眠阶段2的百分比（S2）减少,且实验组的变化程度大于对照组（P<0.05）。两组治疗8周后去甲肾上腺素（NE）、5-羟色胺（5-HT）水平均升高,且实验组的升高程度大于对照组（P<0.05）。两组不良反应发生率组间对比未见差异（P>0.05）。结论：阿戈美拉汀联合舍曲林治疗抑郁症伴失眠,可有效改善抑郁和失眠症状,同时还可调节血清神经递质水平,是一个较为安全可靠的治疗方案。     

Agomelatine strongly interacts with zwitterionic DPPC and charged DPPG membranes

Depression is one of the most common psychiatric diseases in the population. Agomelatine is a novel antidepressant drug with melatonin receptor agonistic and serotonin 5-HT_2C antagonistic properties. Furthermore, being a melatonergic drug, agomelatine has the potential of being used in therapeutic applications like melatonin as an antioxidant, anti-inflammatory and antiapoptotic drug. The action mechanism of agomelatine on the membrane structure has not been clarified yet. In the present study, we aimed to investigate the interaction of agomelatine with model membranes of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylgylcerol (DPPG) by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). We found that agomelatine interacts with the head group in such a manner that it destabilizes the membrane architecture to a large extent. Thus, agomelatine causes alterations in the order, packing and dynamics of the DPPC and DPPG model membranes. Our results suggest that agomelatine strongly interacts with zwitterionic and charged membrane phospholipids. Because lipid structure and dynamics may have influence on the structure of membrane bound proteins and affect the signal transduction systems of membranes, these effects of agomelatine may be important in its action mechanism.     

Synthesis and evaluation of amide side-chain modified Agomelatine analogues as potential antidepressant-like agents

In this work, nineteen analogues of Agomelatine were readily synthesized through structural modification of the acetamide side-chain starting from the key common intermediate 2-(7-methoxynaphthalen-1-yl) ethanamine (3), which was prepared from commercially available compound 2-(7-methoxynaphthalen-1-yl) acetonitrile (2) in two steps. Corticosterone-induced PC12 pheochromocytoma cells phenotypic in vitro model was utilized to evaluate their potential antidepression activities. Imide compound 4a and acylamino carboxylic acid analogue 5b showed good protective effects on traumatic PC12 cells with protection rates of 34.2% and 23.2%, respectively. Further in vivo assessments in C57 mice FST (forced swim test) model demonstrated that compound 4a significantly reduced the immobility time of the tested subjects, indicating antidepressant-like activity. Preliminary toxicity assays conducted on human normal liver L02 cells and embryonic kidney 293 cells suggested a relatively low safety risk for compound 4a compared with the marketed drugs Agomelatine and Fluoxetine. The promising antidepressant-like efficacy of compound 4a, together with the relatively low toxicity to the normal tested cells and high liability of diffusion through the blood–brain barrier (BBB), presents us insights of exploration of me-better drug candidates of Agomelatine.