Das Saibal Kumar, Chakrabarti Ranjan
Metabolic Disorders Group, Dr. Reddy's Laboratories Ltd., Discovery Research, Bollaram Road, Miyapur, Hyderabad 500049, India.
Curr Med Chem. 2006;13(12):1429-60. doi: 10.2174/092986706776872880.
Obesity and its associated morbidities and mortalities are the effects of imbalance between energy intake and expenditure. The healthcare burden for the treatment of obesity is significantly high, due to increased risk of secondary chronic diseases such as hypertension and associated co-morbidities such as diabetes and cardiovascular disease. Lack of physical activity, high fat diets and sedentary life styles are major factors contributing to obesity. However, genetic predisposition and ethnicity are increasingly found to cause obesity. Till date, approved therapeutics have addressed excess energy intake by acting on central neural circuits that regulate feeding or on peripheral mechanisms to reduce nutrient absorption from the gut. These approaches have met with moderate success; and recently with safety concerns, leaving an unmet medical need for effective and safe pharmacotherapy for obesity thereby posing a significant challenge to pharmaceutical industry. Potential antiobesity drugs, which are being investigated by different companies, can be classified in 4 broad categories: 1) Agents that primarily decrease appetite through central action; 2) Agents that primarily increase metabolic rate or affect metabolism through peripheral action; 3) Agents that act on gastrointestinal tract; and 4) Agents that not only affect obesity but also overall Metabolic Syndrome. The current review will deal mainly with different molecules, which are under development for the above-mentioned targets and also their potential benefits and disadvantages.
肥胖及其相关的发病率和死亡率是能量摄入与消耗失衡的结果。由于肥胖会增加患高血压等继发性慢性病以及糖尿病和心血管疾病等相关合并症的风险，因此肥胖治疗的医疗负担非常高。缺乏体育活动、高脂肪饮食和久坐的生活方式是导致肥胖的主要因素。然而，越来越多的研究发现，遗传易感性和种族也会导致肥胖。迄今为止，已获批的治疗方法主要通过作用于调节进食的中枢神经回路或作用于外周机制以减少肠道营养吸收来解决能量摄入过多的问题。这些方法取得了一定的成功；但最近由于安全问题，肥胖症仍存在有效且安全的药物治疗需求未得到满足的情况，这给制药行业带来了重大挑战。不同公司正在研究的潜在抗肥胖药物可大致分为四大类：1）主要通过中枢作用降低食欲的药物；2）主要通过外周作用提高代谢率或影响新陈代谢的药物；3）作用于胃肠道的药物；4）不仅影响肥胖，还影响整体代谢综合征的药物。本综述将主要探讨针对上述靶点正在研发的不同分子，以及它们潜在的优缺点。
