Agomelatine is a selective agonist of melatonin receptor 1A/melatonin receptor 1B(MT/MT)and antagonist of 5-hydroxytryptamine 2C receptors.It is used clinically to treat major depressive episodes in adults.The pro-chr...Agomelatine is a selective agonist of melatonin receptor 1A/melatonin receptor 1B(MT/MT)and antagonist of 5-hydroxytryptamine 2C receptors.It is used clinically to treat major depressive episodes in adults.The pro-chronobiological activity of agomelatine reconstructs sleep-wake rhythms and normalizes circadian disturbances via its agonistic effect of melatonin receptor 1A/melatonin receptor 1B,which work simultaneously to counteract depression and anxiety disorder.Moreover,by antagonizing neocortical postsynaptic 5-hydroxytryptamine 2C receptors,agomelatine enhances the release of dopamine and noradrenaline in the prefrontal cortex,increases the activity of dopamine and noradrenaline,and thereby reduces depression and anxiety disorder.The combination of these two effects means that agomelatine exhibits a unique pharmacological role in the treatment of depression,anxiety,and disturbance of the circadian rhythm.Emotion and sleep are closely related to memory and cognitive function.Memory disorder is defined as any forms of memory abnormality,which is typically evident in a broad range of neurodegenerative diseases,including Alzheimer’s disease.Memory impairment and cognitive impairment are common symptoms of neurodegenerative and psychiatric diseases.Therefore,whether agomelatine can improve memory and cognitive behaviors if used for alleviating depression and circadian-rhythm sleep disorders has become a research“hotspot”.This review presents the latest findings on the effects of agomelatine in the treatment of psychologic and circadian-rhythm sleep disorders in clinical trials and animal experiments.Our review evaluates recent studies on treatment of memory impairment and cognitive impairment in neurodegenerative and psychiatric diseases.展开更多
In the present study,Form I,Form II and Form III of agomelatine were prepared to investigate the variability of polymorphs,then the in-vitro in-vivo correlation were established.The presence of three polymorphs of ago...In the present study,Form I,Form II and Form III of agomelatine were prepared to investigate the variability of polymorphs,then the in-vitro in-vivo correlation were established.The presence of three polymorphs of agomelatine was corroborated through studies by XRPD,TGA and DSC.All the forms obtained were then subjected to the powder and intrinsic dissolution tests.The IDR ranked in the order of Form III>Form I>Form II.Form I and Form III both underwent solvent-mediated phase transformation(SMPT)to Form II during dissolution and the transition points were 62 and 45 min,respectively.Pharmacokinetic profiles were acquired after oral administration of tablets,showing that the ka and AUC0e12 h of Form I,Form II,Form III were 0.580.11,0.340.05,0.740.07 h1 and 296.2549.39,186.0545.93,331.1654.74 ng*h/ml,respectively.Good linearities between IDR and ka,IDR and AUC were established,suggesting that the agomelatine polymorphic forms with faster dissolution rates in-vitro would increase the rate and extent of oral absorption in-vivo.These results demonstrated that IDR was predictive in estimating the relative bioavailability of agomelatine polymorphic forms.展开更多
Nano-NiO and bulk NiO were prepared from Ni(AC)_2·4 H_2O by coordination precipitation using aqueous ammonia and by a solid state reaction, respectively. The nickel oxide particles were characterized by X-ray Dif...Nano-NiO and bulk NiO were prepared from Ni(AC)_2·4 H_2O by coordination precipitation using aqueous ammonia and by a solid state reaction, respectively. The nickel oxide particles were characterized by X-ray Diffraction(XRD) and scanning electron microscopy(SEM). The results indicate that nano-sized NiO has a crystal phase with a standard face-centered cubic lattice structure, with a mean particle diameter of about 10 nm. The evaluation of the activity of nickel oxide nanoparticles in the catalytic hydrogenation of 7-methoxy-1-naphthylacetonitrile was carried out. The results demonstrate the efficient synthesis of the title compound by a one-pot catalytic hydrogenation and acetylation with NiO. The NiO nanoparticles displayed superior catalytic activity in the synthesis of agomelatine in the one-pot reaction.The total yield of agomelatine is over 81.8% with a purity of 99.2%, as determined by HPLC. The structure of agomelatine was confirmed by IR, MS, and 1 H NMR analysis.展开更多
The aim of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of ago...The aim of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of agomelatine in Chinese healthy male subjects. This was performed in a single-dose, randomized-sequence, open-label, four-way crossover study with a one-day washout period between doses. Healthy Chinese males were randomly assigned to receive 25 mg of either the test or reference formulation. The formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios and ratio of geometric means (GMR) of AUC and C m of agomelatine were within the predetermined bioequivalence range based on RSABE method. Results showed that both of the 90% CIs for the log-transformed ratios of AUC and C-max of 7-desmethyl-agomelatine and 3-hydroxyagomelatine were within the predetermined bioequivalence range. The 90% CIs for natural log transformed ratios of C-max, AUC(0-t), and AUC(0-infinity) of agomelatine (104.42-139.86, 101.33-123.83 and 97.90-117.94) were within the RSABE acceptance limits, and 3-hydroxy-agomelatine (105.55-123.03, 101.95-109.10 and 101.72-108.70) and 7-desmethyl-agomelatine (104.50-125.23, 102.36-111.50 and 101.62-110.64) were within the FDA bioequivalence definition intervals (0.80-1.25 for AUC and 0.75-1.33 for C-max). The RSABE approach was successful in evaluating the bioequivalence of these two formulations. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.展开更多
目的:系统评价阿戈美拉汀与度洛西汀治疗首发抑郁障碍患者的疗效和安全性的差异。方法:运用中国知网(CNKI)、维普(VIP)、万方、PubMed、Web of Science等数据库进行检索,纳入两种药物治疗首发抑郁障碍的头对头临床随机对照研究,提取疗...目的:系统评价阿戈美拉汀与度洛西汀治疗首发抑郁障碍患者的疗效和安全性的差异。方法:运用中国知网(CNKI)、维普(VIP)、万方、PubMed、Web of Science等数据库进行检索,纳入两种药物治疗首发抑郁障碍的头对头临床随机对照研究,提取疗效和安全性的数据,采用RevMan 5.4进行meta分析。结果:共纳入6篇文章。meta分析结果显示,治疗后阿戈美拉汀组与度洛西汀组HAMD-17评分差异(P<0.05)、总有效率差异(P=0.002)有统计学意义,治愈率差异(P=0.10)、总不良反应发生率差异(P=0.11)无统计学意义。结论:与度洛西汀相比,阿戈美拉汀治疗首发抑郁障碍的安全性相当,疗效具有优势。展开更多
基金supported by Shanxi“1331 Project”Key Subjects Construction,No.1331KSC(to JSQ)Science Research Start-up Fund for Doctors of Shanxi Province,No.SD2011(to TL)Science Research Start-Up Fund for Doctors of Shanxi Medical University,No.XD2017(to TL)。
文摘Agomelatine is a selective agonist of melatonin receptor 1A/melatonin receptor 1B(MT/MT)and antagonist of 5-hydroxytryptamine 2C receptors.It is used clinically to treat major depressive episodes in adults.The pro-chronobiological activity of agomelatine reconstructs sleep-wake rhythms and normalizes circadian disturbances via its agonistic effect of melatonin receptor 1A/melatonin receptor 1B,which work simultaneously to counteract depression and anxiety disorder.Moreover,by antagonizing neocortical postsynaptic 5-hydroxytryptamine 2C receptors,agomelatine enhances the release of dopamine and noradrenaline in the prefrontal cortex,increases the activity of dopamine and noradrenaline,and thereby reduces depression and anxiety disorder.The combination of these two effects means that agomelatine exhibits a unique pharmacological role in the treatment of depression,anxiety,and disturbance of the circadian rhythm.Emotion and sleep are closely related to memory and cognitive function.Memory disorder is defined as any forms of memory abnormality,which is typically evident in a broad range of neurodegenerative diseases,including Alzheimer’s disease.Memory impairment and cognitive impairment are common symptoms of neurodegenerative and psychiatric diseases.Therefore,whether agomelatine can improve memory and cognitive behaviors if used for alleviating depression and circadian-rhythm sleep disorders has become a research“hotspot”.This review presents the latest findings on the effects of agomelatine in the treatment of psychologic and circadian-rhythm sleep disorders in clinical trials and animal experiments.Our review evaluates recent studies on treatment of memory impairment and cognitive impairment in neurodegenerative and psychiatric diseases.
基金The authors acknowledge the financial support received from the National Science and Technology Major Projects for Major New Drugs Innovation and Development of China(No.2009ZX09501-022).
文摘In the present study,Form I,Form II and Form III of agomelatine were prepared to investigate the variability of polymorphs,then the in-vitro in-vivo correlation were established.The presence of three polymorphs of agomelatine was corroborated through studies by XRPD,TGA and DSC.All the forms obtained were then subjected to the powder and intrinsic dissolution tests.The IDR ranked in the order of Form III>Form I>Form II.Form I and Form III both underwent solvent-mediated phase transformation(SMPT)to Form II during dissolution and the transition points were 62 and 45 min,respectively.Pharmacokinetic profiles were acquired after oral administration of tablets,showing that the ka and AUC0e12 h of Form I,Form II,Form III were 0.580.11,0.340.05,0.740.07 h1 and 296.2549.39,186.0545.93,331.1654.74 ng*h/ml,respectively.Good linearities between IDR and ka,IDR and AUC were established,suggesting that the agomelatine polymorphic forms with faster dissolution rates in-vitro would increase the rate and extent of oral absorption in-vivo.These results demonstrated that IDR was predictive in estimating the relative bioavailability of agomelatine polymorphic forms.
基金Funded by the Natural Science Foundation of Hubei Province(2017CFB680)the Hubei University of Science and Technology Nuclear Technology Special Project(2018-19KZ06)+1 种基金the Open Fund of the State Key Laboratory of Refractories and Metallurgy(Wuhan University of Science and Technology)of China(G201703)the Key Laboratory of Measurement and Control System for Offshore Environment,Fuqing Branch of Fujian Normal University,Fujian Province University(S1-KF1604)
文摘Nano-NiO and bulk NiO were prepared from Ni(AC)_2·4 H_2O by coordination precipitation using aqueous ammonia and by a solid state reaction, respectively. The nickel oxide particles were characterized by X-ray Diffraction(XRD) and scanning electron microscopy(SEM). The results indicate that nano-sized NiO has a crystal phase with a standard face-centered cubic lattice structure, with a mean particle diameter of about 10 nm. The evaluation of the activity of nickel oxide nanoparticles in the catalytic hydrogenation of 7-methoxy-1-naphthylacetonitrile was carried out. The results demonstrate the efficient synthesis of the title compound by a one-pot catalytic hydrogenation and acetylation with NiO. The NiO nanoparticles displayed superior catalytic activity in the synthesis of agomelatine in the one-pot reaction.The total yield of agomelatine is over 81.8% with a purity of 99.2%, as determined by HPLC. The structure of agomelatine was confirmed by IR, MS, and 1 H NMR analysis.
基金supported by the National Natural Science Foundation of China(No.81102499)Hunan Science and Technology Project(No.2011SK3261)+1 种基金the Fundamental Research Funds for the Central Universities of Central South University(No.2014zzts313)the support from Chongqing Fu An Pharmaceutical Group Qingyutang Pharmaceutical Co.,Ltd
文摘The aim of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of agomelatine in Chinese healthy male subjects. This was performed in a single-dose, randomized-sequence, open-label, four-way crossover study with a one-day washout period between doses. Healthy Chinese males were randomly assigned to receive 25 mg of either the test or reference formulation. The formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios and ratio of geometric means (GMR) of AUC and C m of agomelatine were within the predetermined bioequivalence range based on RSABE method. Results showed that both of the 90% CIs for the log-transformed ratios of AUC and C-max of 7-desmethyl-agomelatine and 3-hydroxyagomelatine were within the predetermined bioequivalence range. The 90% CIs for natural log transformed ratios of C-max, AUC(0-t), and AUC(0-infinity) of agomelatine (104.42-139.86, 101.33-123.83 and 97.90-117.94) were within the RSABE acceptance limits, and 3-hydroxy-agomelatine (105.55-123.03, 101.95-109.10 and 101.72-108.70) and 7-desmethyl-agomelatine (104.50-125.23, 102.36-111.50 and 101.62-110.64) were within the FDA bioequivalence definition intervals (0.80-1.25 for AUC and 0.75-1.33 for C-max). The RSABE approach was successful in evaluating the bioequivalence of these two formulations. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
文摘目的:系统评价阿戈美拉汀与度洛西汀治疗首发抑郁障碍患者的疗效和安全性的差异。方法:运用中国知网(CNKI)、维普(VIP)、万方、PubMed、Web of Science等数据库进行检索,纳入两种药物治疗首发抑郁障碍的头对头临床随机对照研究,提取疗效和安全性的数据,采用RevMan 5.4进行meta分析。结果:共纳入6篇文章。meta分析结果显示,治疗后阿戈美拉汀组与度洛西汀组HAMD-17评分差异(P<0.05)、总有效率差异(P=0.002)有统计学意义,治愈率差异(P=0.10)、总不良反应发生率差异(P=0.11)无统计学意义。结论:与度洛西汀相比,阿戈美拉汀治疗首发抑郁障碍的安全性相当,疗效具有优势。
