药物减肥机制研究概述

目的：寻找有效安全的减肥药物。方法：查阅国内外献，探讨药物减肥的不同作用机制(作用于中枢或外周)。结果：各类药物通过作用不同靶点起作用，对临床治疗肥胖具有重要意义。结论：有助于研制和开发新型、有效、安全的减肥药物，临床医师可根据不同的作用机制选用合适的药物治疗肥胖，从而达到合理用药的目的。     

减肥药研发:窘境背后的希望

肥胖严重威胁着人们的健康,已经成为全球性的流行病。由于目前能有效治疗肥胖的手段有限,肥胖难以得到有效控制。由于药物的不良反应问题,已上市的减肥药大部分都被淘汰,肥胖正在面临无药可治的窘迫局面。人体中有许多靶点能够起到调节能量代谢,控制体重的作用。作用于这些靶点的减肥药物正在研发中。本文综述了治疗肥胖相关的药物靶点和作用机制以及减肥药物的研发现状。     

减肥药物的研究进展及前景

目的寻找有效安全的减肥药物。方法查阅国内外文献,了解不同类减肥药物的进展和作用特点．结果各类药物对临床治疗肥胖具有一定重要的意义。结论研制和开发新型、有效、安全的减肥药物,临床医师可根据不同的作用机制选用合适的药物治疗肥胖,从而达到合理用药的目的。     

肥胖2型糖尿病药物研究进展

肥胖与糖尿病发病率密切相关，是糖尿病发病率上升的重要原因。如今上市的大部分降糖药物如胰岛素及其类似物、胰岛素促泌剂、胰岛素增敏剂等都会不同程度的增加患者体重，从而加重胰岛素抵抗，增加降糖药物剂量，形成恶性循环，降糖兼具减肥是当今糖尿病新药研发重要趋势。本文概述了肥胖2型糖尿病的流行病学以及目前上市的降糖药物对体重发展的影响，并重点概述了兼具减肥效应的降糖药物的最新靶点，为肥胖2型糖尿病患者的治疗提供潜在新方法。     

六种药物新靶点的研究

某些疾病用药后往往疗效低、易复发，原因在于治疗药物未能直抵病灶——药物靶点。以下为六种药物新靶点初探。     

北京人的“瘦身”状况

北京美兰德信息公司医药调研部于今年九月初针对北京市区15—54岁居民进行了一次关于肥胖和减肥行为的调查研究。本次调查采用电话调查、网上调查和专家访问相结合的方法进行,共获取有效样本818人。调查结果表明,北京市区15—54岁的肥胖人口约有93万人,曾经或正在减肥的有120万人,58万人采用药物减肥。 5个人中一个胖子 本次调查引入亚太地区标准体重指数[BMI=体重(公斤)/身高(米)2]。     

糖尿病微血管并发症的机制研究与防控

对糖尿病并发症的始动机制、药物作用靶点的不明确是导致糖尿病并发症治疗药物众多,但真正能实现靶点定向治疗的药物缺少的主要原因。     

基于病毒靶点的乙型肝炎的抗病毒药物研究进展

乙型肝炎病毒(HBV)感染是导致肝硬化和肝癌的主要原因,抗病毒是治疗慢性乙型肝炎的关键.目前用于治疗HBV感染的药物主要集中于干扰素和核苷类似物,但效果并不十分令人满意.因此,寻找具有新的靶点和作用机制的抗HBV药物至关重要.文中对近年来发展的部分抗HBV药物的作用靶点和作用机制进行综述.     

lncRNA作为抗肿瘤药物新靶点的机制及其研究进展

目的综述lncRNA作为抗肿瘤药物新靶点的机制及其研究进展,揭示其研究趋势及方向。方法查阅近年来国内外相关文献,进行分析总结。结果与结论 lncRNA在肿瘤发生和发展中具有多重调节作用,以lncRNA为靶点开发抗肿瘤新药必将成为未来抗肿瘤药物研发的新趋势。     

针刺治疗单纯性肥胖73例临床观察

单纯性肥胖是人体内热量的摄入大于消耗和利用，造成脂肪在体内积聚，导致体重超常的病症。随着我国经济的发展，人民生活习惯的改变及饮食结构的变化，肥胖人口数蛰也呈急剧上升趋势。肥胖不仅影响人们外观形体的审美，更严重的是它危害人体的健康，是脂质代谢紊乱、冠心病、2型糖尿病、心脑血管病的危险因素。目前肥胖已成为严重威胁人类身心健康的全球性疾病，减肥已成为热门课题．减肥方法较多。针灸作为一种非药物疗法且效果显著．在临床已得到广泛运用。笔者收集了112例肥胖病人．其中73例用针刺治疗．取得较好的效果。     

Is the cannabinoid CB1 receptor antagonist rimonabant advancing the treatment of obesity?

Orlistat and sibutramine are the most commonly used drugs in the reduction of body weight, but both of these result in only modest weight reduction. In diet-induced obesity of the mouse, the cannabinoid CB1 receptor antagonist rimonabant induced a marked, sustained reduction of body weight and obesity. In the first major clinical trial (Rimonabant in Obesity), patients were put on a hypocaloric diet, which lead to weight loss of 3.6 kg after 1 year. This weight loss was increased to 8.6 kg by treatment with rimonabant 20 mg/day for the year. Discontinuations due to nausea, vomiting, diarrhoea and headache were more common in the rimonabant 20 mg/day group than the placebo group, but occurred in very few patients. Rimonabant is an addition to the available drugs for the treatment of obesity.     

Sibutramine Effects on Central Mechanisms Regulating Energy Homeostasis

During the last 50 years the global pandemic of obesity and associated life-threatening co-morbidities strongly promoted the development of anti-obesity pharmacotherapy. Sibutramine is an anti-obesity drug that in conjunction with lifestyle modifications reduces food intake and body weight. This may result from several effects: inhibition of presynaptic reuptake of monoaminergic neurotransmitters in the central nervous system, thereby suppressing appetite, induction of an increase in anorexigenic and a decrease in orexigenic neuropeptide secretion, induction of an increase in energy expenditure, and induction of peripheral sympathomimetic effects. The effects of sibutramine on anabolic and catabolic signals that regulate energy homeostasis in the hypothalamus are not completely understood. So, the aim of this review is to summarize the central mechanisms of action of sibutramine, responsible for its weight and food intake reducing potential. Despite being a useful drug in obesity treatment, awareness about the loss of long-term effectiveness and detrimental side effects of sibutramine has recently emerged. As a consequence, new drugs that produce safer and more persistent weight loss are currently undergoing clinical trials.     

Nicotine,body weight and potential implications in the treatment of obesity

Obesity is an epidemic problem in the U. S. and many other industrialized nations. Historically, the drugs used for the treatment of obesity generally targeted small molecule neurotransmitters. As research grows to decipher the underlying molecular mechanisms behind energy homeostasis, it is becoming evident that the modulating effects of neuropeptides also are critical in the regulation of appetite and metabolism. The search for drugs to modify these monoaminergic and peptidergic pathways may eventually prove successful in the treatment of obesity. While tobacco smoking has long been used as one strategy to maintain a lower body weight, especially in female smokers, its adverse associations with addiction and disease overshadow its potential use as an antiobesity agent. Potential pharmacological effects of nicotine could be better understood as the intricacies of the nicotinic acetylcholine receptor are revealed. The objective of this review is threefold: first is to provide an overview of the physiological effects of nicotine on body weight while focusing on the drugs that are available as antiobesity and smoking cessation agents. Second is to provide the present status of the nicotinic acetylcholine receptor as it relates to energy homeostasis and its potential as an effective treatment modality for obesity. Third is to present the current knowledge with respect to nicotine's effects on energy homeostatic and reward related pathways at the molecular level. A better understanding of the regulatory mechanisms underlying the pharmacological effects of nicotine on body weight will provide insights in identification of potential targets for the development of appropriate medicines in the treatment of obesity.     

Current and novel approaches to the drug therapy of obesity

Introduction Obesity has been described as the greatest current threat to human health. Although diet and lifestyle changes remain the cornerstones of therapy for obesity, weight losses are often small, and long-term success is disappointing.Discussion When these lifestyle-modifying attempts fail, the use of anti-obesity drugs is warranted. Drug treatment is often indicated, but is somewhat limited by the minimal number of well-tolerated drugs that have proven to have long-term efficacy in maintaining body weight loss. The currently available drugs, sibutramine and orlistat, appear modestly effective in promoting weight loss. However, pharmacological therapy for obesity is in transition; expanding knowledge of the physiological mechanisms of body weight regulation has revealed new molecular targets, and more than 150 novel agents are under active development.Conclusions Because weight regulation is complex, and redundant systems protect against perceived starvation, optimal treatment of obesity will likely require combinations of therapies. In addition, a better comprehension of the problem prior to its treatment would be preferable before targeting homeostatic pathways which could be irrelevant.     

Neuronal histamine and its receptors: implication of the pharmacological treatment of obesity

Obesity is the effect of imbalance between energy intake and expenditure and forms a fundamental basis of the metabolic syndrome. A number of substances implicated in the regulation of energy metabolism represent opportunities for anti-obesity drug development. Neuronal histamine and its receptors have been shown to regulate energy metabolism and are considered as anti-obesity targets. Several histamine receptor subtypes have been identified; of these, histamine H1 and H3 receptors (H1-R and H3-R) have been specifically recognized as mediators of energy intake and expenditure. In addition, several histamine drugs related to H1-R and H3-R, have been shown to attenuate body weight gain both in rodent and human. These results provide the reagents for histamine receptors biology and may find applications in the treatment of obesity and related metabolic disorders. In this review, the development of agonists and antagonists of histamine receptors are provided.     

The ineluctable constraints of thermodynamics in the aetiology of obesity

We exploit the detail‐independence feature of thermodynamics to examine issues related to the development of obesity. We adopt a ‘global’ approach consistent with focus on the first law of thermodynamics – namely that the metabolic energy provided by dietary foodstuffs has only three possible fates: the performance of work (be it microscopic or macroscopic), the generation of heat, or storage – primarily in the form of adipose tissue. Quantification of the energy expended, in the form of fat metabolised, during selected endurance events, reveals the inherent limitation of over‐reliance on exercise as a primary agent of weight loss. This result prompts examination of various (non‐exercise based) possibilities of increasing the rate of heat loss. Since these, too, give little cause for optimism, we are obliged to conclude that obesity can be prevented, or weight loss achieved, only if exercise is supplemented by reduction of food intake.     

Obesity and the hepatic control of feeding behavior

Despite its well-established role in the control of food intake, the liver has not been a target for the development of drugs to modulate appetite and treat obesity. This paper provides an overview of the hepatic control of food intake and focuses in particular on how it may play a part in overeating and body weight gain. Signals from the liver that control feeding behavior are triggered in response to changes in liver energy status and are carried to the brain by vagal sensory neurons. Consumption of diets rich in fat and carbohydrate is a major contributing cause of overeating and obesity, and susceptibility to such diet-induced obesity is associated with a reduced capacity for fat oxidation. Inhibition of fatty acid oxidation in the liver stimulates food intake by decreasing liver ATP production, suggesting that low liver energy status may contribute to diet-induced overeating and obesity. These findings raise the possibility that liver energy production, the mechanisms that transduce changes in hepatic energy status into neural signals or hepatic vagal afferent activity may provide new targets for the development of drugs for appetite control and obesity.     

Emerging drugs for the treatment of obesity

Introduction: The increasing prevalence of obesity represents a huge threat to public health and the current pharmacological treatment options are limited. Bariatric surgery is by far the most effective treatment for severe obesity, highlighting the urgent need for new and improved drug therapies.

Areas covered: Based on the physiological regulation of energy homeostasis, pharmacological strategies to treat obesity are evaluated with focus on drugs in phase 2 and 3 clinical development. The potential impact of these drugs on current treatment standards and the barriers for development are discussed and set in a historical perspective of previous antiobesity medications.

Expert opinion: The radical effects of bariatric surgery have extended our understanding of the mechanisms controlling appetite and boosted the search for new drug targets in obesity treatment. Accordingly, several compounds targeting the central nervous system and/or periphery are in pipeline for obesity. These drugs should be evaluated over a wide array of end-points; in particular, long-term safety monitoring is necessary as serious adverse events may appear. Combination therapy targeting more than one pathway controlling energy balance might be necessary to achieve substantial weight loss while minimising side effects.     

The fatty acid oxidation pathway as a therapeutic target for insulin resistance

It is recognised that obesity is a major driver for insulin resistance and Type 2 diabetes in both adult and young members of diverse societies. Weight loss strategies involving diet, exercise and behaviour modification work only for the minority of highly motivated individuals, but fail completely in the vast majority; yet weight loss is associated with benefits in metabolic health. Why is it so difficult to maintain weight loss in the longer term? Here, the authors explore the possibility that energy partitioning, especially of lipids, plays a key role in both weight recidivism and, by association, insulin resistance. Drug targets that address key pathways important in this process, where progress in drug discovery is apparent, are discussed.     

The fatty acid oxidation pathway as a therapeutic target for insulin resistance

It is recognised that obesity is a major driver for insulin resistance and Type 2 diabetes in both adult and young members of diverse societies. Weight loss strategies involving diet, exercise and behaviour modification work only for the minority of highly motivated individuals, but fail completely in the vast majority; yet weight loss is associated with benefits in metabolic health. Why is it so difficult to maintain weight loss in the longer term? Here, the authors explore the possibility that energy partitioning, especially of lipids, plays a key role in both weight recidivism and, by association, insulin resistance. Drug targets that address key pathways important in this process, where progress in drug discovery is apparent, are discussed.