减肥药:一座潜在的金山

据美国疾病控制中心报道，目前全美肥胖患者已逾440万，而在诺大的肥胖者人群中，接受处方药治疗的患者人数仅占1％。显然，这个尚未开垦的处女地对生物技术和制药公司极具诱惑力，各大公司纷纷跻身开发新减肥药的行列。有关统计数字显示，美国现有70多家公司的180种减肥药正在试验中。     

减肥药的合理应用

对肥胖的概念、肥胖带来的后果以及药物治疗进行了阐述.     

减肥药的作用新靶点及相关新药研发近况

对近年来发现的减肥药作用新靶点，如瘦素及其受体、睫状神经营养因子、大麻素受体、神经肽Y5受体、β3肾上腺素受体、脂肪酸转运蛋白4等进行了介绍，并对以这些新靶点为基础开发的一系列相关新药的研究进展进行了综述。     

减肥药的研究进展

由于遗传、生活方式及饮食结构不合理等方面的原因,肥胖症患者日益增多,"减肥"成为了热门话题,同时医学领域也兴起一股减肥药的研发热潮.本文在查阅了相关资料的基础上,从作用机制、副作用等方面对曾经产生过较大影响的一些减肥药进行了系统的分析,并对未来减肥药的走势做出了推断,以期能够对减肥药未来的发展、完善提供可供参考的依据.     

减肥药的不良反应及正确使用

肥胖与多种疾病相关联,“死亡五重奏”:高血压、高血脂、糖尿病、冠心病、脑卒中的发病已被证明与超重(肥胖)有关。研究还提示包括骨关节病变和龋齿在内的疾病均与肥胖相关,对肥胖是一种疾病的看法已成共识。随着肥胖、超重患者的增多,加上部分非肥胖超重患者对体型美的要求,减肥药物在不同的场合被广泛应用。但是滥用减肥药的情况也时有发生,因应用减肥药物出现各种不良反应,甚至死亡的报道屡屡见诸于各种媒体,因此了解减肥药的作用及副作用,合理使用减肥药十分重要。     

肥胖与减肥药的现状及评价

肥胖在美国已成为除吸烟以外第二个可预防的死亡原因.据估计,在美国有5800万人患肥胖症,每年30万人的死亡与肥胖有关.在过去的10～20年间,美国成年人肥胖发生率从8%增加到26%,又上升至33.4%.肥胖作为一种慢性疾病的发病率正逐年增加.目前的研究认为,不同的人在完全相同的环境下,体重以不同的速度增加,其增加的数量由遗传决定.也有人认为,人类在发展过程中,我们的祖先获得了能够使机体从每一餐中储存脂肪的能力,以度过可能出现饥荒的"三十个基因".而在现在高脂、高热量的饮食环境下,这"三十个基因"变成了累赘.当人体进食热量多于消耗热量时,多余热量即以脂肪形式储存于体内,因体脂增加而使体重指数(BMI)[BMI=体重(kg)/身高(m)2]大于24者即称为肥胖症.如无明显病因的称为单纯性肥胖症,若有明确病因者称为继发性肥胖症.单纯性肥胖是肥胖症中最常见的一种,不仅影响美观,而且易患高血压、冠心病、Ⅱ型糖尿病、中风、肝胆疾病、骨关节炎、睡眠窒息、呼吸疾病及某些癌症,对它的防治有着十分重要的临床意义.     

信号传导分子作为药物设计的靶点

近１０多年间分子生物学技术的爆炸式发展,确实并克隆许多调节正常生理功能的蛋白质,部分阐明了它们在疾病状态下的作用,许多疾病与信号传导途径异常有关,因此信号分子可以作为治疗药物设计的靶点,这年来已经成功应用于Ｒａｓ法尼基化合物作为肿瘤抑制剂,ＪＡＫ２阻断剂中作为治疗前Ｂ细胞急性淋巴细胞白血病的有效药物,本简述近年来有关信号传导分子作为疾病的靶点的研究进展。     

美国FDA上市减肥药不良反应研究进展与安全性思考

本文综述了1887年至今获得美国FDA批准上市的17种减肥药在临床试验期间及上市后的相关不良反应,包括仍在市的6种以及因瓣膜性心脏病、自杀倾向、致癌风险等原因遭撤市的11种减肥药。减肥药在降低肥胖患者体重以及代谢获益的同时也会引发各种不良反应,包括精神神经系统不良反应、致癌风险、心脏毒性、肝损伤、胰腺毒性、肾毒性、消化道不良反应等诸多不良反应;其中,美国FDA会对严重不良反应进行黑框警告,而具有致命性的严重不良反应药物则被勒令撤市。本文在归纳减肥药不良反应的同时对其安全性进行深度思考,以期为减肥药的研发及临床医生与患者正确使用减肥药提供相关参考,保护人民生命健康。     

减肥药—制药公司盈利的机会

一份研究报告提到，到2012年全球抗肥胖药的市场规模估计将达到25亿美元，目前为5．26亿。对于日益增长的肥胖问题新药未必是最佳的解决办法，良好的饮食控制和运动仍然具有重要意义。与肥胖有关的健康问题和共发病吸走了世界各国巨大的国家医疗保健预算。     

The obesity pipeline: current strategies in the development of anti-obesity drugs

This review provides a summary of currently available pharmaceutical therapies for the treatment of obesity, along with an overview of the pipeline of products currently in development, and the key mechanisms on which the major development candidates are based. In particular, the recent increase in understanding of the role of gut peptides in energy homeostasis is highlighted as a promising source of potential future obesity therapies.     

减肥药物最新研究进展

减肥药物按作用机制可分为3类：抑制食欲药物、抑制肠道消化吸收药物和增加能量消耗药物。现分别介绍上述各类中的代表性药物和正处于临床或临床前研究阶段、有开发前景的药物的最新研究进展。     

Clinical evaluation of anti-obesity drugs

Obesity is a major health problem and as a result, it is reasonable to consider pharmacological approaches alongside approaches involving diet, physical activity and lifestyle change. The currently available drugs, sibutramine and orlistat, result in modest, clinically worthwhile weight loss, with demonstrable improvements in co-morbidity, but do not meet the often unrealistic expectations of patients or health care professionals managing obese patients. There is insufficient data on efficacy or safety of other agents to support their use. Many new pharmacological approaches are under investigation. These include gut hormones, such a peptide YY (3-36) and cholecystokinin that normally signal satiety, and centrally-acting agents such as serotonin agonists, the anticonvulsants topiramate and zonisamide, cannabinoid receptor antagonists and drugs that act on other peptide neurotransmitter systems such as NPY and the melanocortins. Given the multiple pathways that influence energy balance, it is likely that therapies targeting more than one control system may be required in the future to meet the expectations and needs of patients needing to lose weight for medical reasons.     

治疗肥胖症的药物研究进展

从能量摄入和能量支出2个角度综述了目前国际上正在研究开发的治疗肥胖的靶分子。调节能量摄入的中枢神经系统靶分子主要有leptin和神经肽，外周的调节能量摄入的靶分子主要是一些胃肠肽。肾上腺素β3受体激动剂由于可增加能量支出，刺激机体产热也是引人注意的靶分子。     

减肥药的安全性与合理使用

肥胖是由于能量摄入超过消耗,多余的能量以脂肪的形式储存起来,其量超过正常生理需要,且达到一定水平则称为肥胖症。据泛美卫生组织最近的调查报告显示,随着世界经济全球化,威胁人类健康的肥胖症迅速增加。如在美国,2/3的成人体重     

Inhibitors of absorption as anti-obesity drugs]

There are two types of anti-obesity agents which are classified as inhibitors of absorption: inhibitors of lipid and carbohydrate absorption. Inhibitors of lipid absorption consist of lipase inhibitor (orlistat, Nomma Herb's extract (CT-II) and fat substitute (olestra, sucrose polyester). Orlistat is now available as an anti-obesity drug in the USA and Europe. CT-II may be useful as a functional diet. Application of fat substitute is still limited in snack food. As for inhibitors of carbohydrate absorption, alpha-glucosidase inhibitors are now available as anti-diabetic drugs. To develop these agents for anti-obesity drug, solution of adverse effects on the gastrointestinal tract are necessary.     

A risk-benefit assessment of anti-obesity drugs.

This review evaluates the benefits and potential health risks of the currently used drugs that are approved for the pharmacological treatment of obesity. Analysis of several long term clinical trials indicates that all of these drugs are efficient in reducing excess bodyweight, and that the majority of them allow the maintenance of the reduced bodyweight for at least 1 year. However, the loss of bodyweight attributable to these drugs is in general rather modest, approaching only 0.2 kg per week during the first 6 months of treatment, and at least a partial regain of bodyweight occurs when these drugs are used for periods longer than 1 year. All of these drugs induce several adverse effects. Although most of these adverse effects are mild and transient, the prolonged use of adrenergic or serotonergic anorectic drugs, or their use as combination treatment, may induce serious and potentially life-threatening complications, such as primary pulmonary hypertension or valvular heart disease. The adrenergic appetite-suppressing drugs are not recommended for the treatment of obesity, since their safety has never been evaluated in long term clinical trials, and because of their stimulatory effects on the cardiovascular and nervous systems. The serotonergic drugs, such as fenfluramine and dexfenfluramine, have been the most widely used during the past decade; however, both these compounds have recently been withdrawn from the market, since their use was associated with serious cardiovascular complications. The safety of the prolonged therapeutic use of newer compounds such as sibutramine and orlistat has not yet been demonstrated. Therefore, none of the currently available anti-obesity medications meets the criteria of an 'ideal anti-obesity drug' and, if prescribed, these medications should be used with caution and only under careful medical supervision. Since obesity is recognised as a chronic health-threatening condition, and since classical behavioural therapeutic approaches lack long term efficacy, there is clearly a need for an efficient pharmacological treatment offering an acceptable safety profile. Such a treatment is not available at present. Development of new agents and a more careful assessment of the safety of currently available drugs are needed.     

Development of anti-obesity agents: drugs that target neuropeptide and neurotransmitter systems

Background: Obesity results from an imbalance of energy intake and energy expenditure. While the prevalence of obesity is increasing and the negative impact on public health is being recognized, highly effective and safe therapy for obesity is not yet available. Objective: This review summarizes the current state of the art in the late-stage development area of anti-obesity drugs, provides a framework for understanding the potential disparity of animal data and human disease modification for some agents, and highlights novel agents that may provide significant clinical benefits in the future. Methods: Published literature and meeting proceedings were surveyed to review the late-stage development of new anti-obesity agents. Results/conclusions: Most of the current clinical candidates for obesity treatment are targeting neurotransmitter receptors or peptide receptors. While new agents have been discovered, a significant failure rate also emerged. Rigorous scientific investigations, developing target engagement tools, and understanding any potential rodent versus human species difference will be necessary to ascertain mechanism-based efficacy and increase the probability of success.     

抗肥胖药物发展现状及研究进展

肥胖已成为全球性的重要公共卫生问题之一.不过,尽管肥胖流行且会带来一系列的健康相关疾病风险,但现可供患者选择的抗肥胖药物却仅主要有盐酸芬特明、盐酸安非拉酮和奥利司他这3个,远远不能满足临床的需要.为此,制药公司正在积极致力研究与开发新的抗肥胖药物,以期能够更安全、更有效地治疗肥胖并减少肥胖相关疾病风险.其中,劳卡色林和...