Zieba Remigiusz
Zakład Farmakodynamiki, Uniwersytet Medyczny w Łodzi, Łódź.
Postepy Hig Med Dosw (Online). 2007 Oct 19;61:612-26.
This review summarizes data on currently used antiobesity drugs and new compounds under clinical development. Three antiobesity drugs are currently accepted for long-term use. Sibutramine is a noradrenaline and serotonin reuptake inhibitor which reduces body weight by about 4-5 kg but increases heart rate and arterial blood pressure. Orlistat is a gastrointestinal lipase inhibitor which results in mean weight loss by about 3 kg and reduces the incidence of type 2 diabetes in patients with impaired glucose tolerance; however, adverse gastrointestinal effects have been observed. Rimonabant is an endocannabinoid CB1 receptor antagonist which induces a 4-5 kg mean weight loss and improves glycemic and lipid profiles, but it induces anxiety and depressive disorders. Unfortunately, there are no data on the chronic administration of these drugs. Other drugs can induce weight loss, e.g. some antidepressants, antiseizure agents, and antidiabetic drugs. The moderate efficacy of currently used antiobesity drugs has led to an intense effort to identify new, safe antiobesity drugs with better therapeutic profiles. The new antiobesity drugs under clinical development include: 1) agents that affect neurotransmitters in the central nervous system, including noradrenaline and dopamine reuptake inhibitors (bupropion, radafaxine), selective 5HT2C receptor agonists (lorcaserin), and selective 5HT6 receptor antagonists, 2) agents that modulate the activity of neuropeptides influencing food intake, including leptin analogues, human ciliary neurotrophic factor (Axokine), neuropeptide Y antagonists, and melanine-concentrating hormone antagonists, 3) agents that affect the peripheral satiety signals and brain-gut axis, e.g. selective cholecystokinin receptor A agonists, PYY3-36, agents decreasing ghrelin activity, 4) thermogenic agents, e.g. selective beta3 receptor agonists and selective thyroid hormone receptor beta agonists, and 5) others, e.g. human growth hormone fragment (AOD9604) and gastrointestinal lipase inhibitor (cetilistat).
本综述总结了目前使用的抗肥胖药物以及正在进行临床开发的新化合物的数据。目前有三种抗肥胖药物被批准长期使用。西布曲明是一种去甲肾上腺素和5-羟色胺再摄取抑制剂，可使体重减轻约4 - 5千克，但会增加心率和动脉血压。奥利司他是一种胃肠道脂肪酶抑制剂，可使平均体重减轻约3千克，并降低糖耐量受损患者患2型糖尿病的发生率；然而，已观察到其有不良胃肠道反应。利莫那班是一种内源性大麻素CB1受体拮抗剂，可使平均体重减轻4 - 5千克，并改善血糖和血脂状况，但会引发焦虑和抑郁障碍。遗憾的是，尚无这些药物长期给药的数据。其他药物也可导致体重减轻，如一些抗抑郁药、抗癫痫药和抗糖尿病药。目前使用的抗肥胖药物疗效一般，因此人们一直在努力寻找新的、安全的、具有更好治疗效果的抗肥胖药物。正在进行临床开发的新型抗肥胖药物包括：1）影响中枢神经系统神经递质的药物，包括去甲肾上腺素和多巴胺再摄取抑制剂（安非他酮、瑞波西汀）、选择性5HT2C受体激动剂（洛卡塞林）以及选择性5HT6受体拮抗剂；2）调节影响食物摄入的神经肽活性的药物，包括瘦素类似物、人睫状神经营养因子（Axokine）、神经肽Y拮抗剂以及促黑素聚集激素拮抗剂；3）影响外周饱腹感信号和脑 - 肠轴的药物，如选择性胆囊收缩素A受体激动剂、PYY3 - 36、降低胃饥饿素活性的药物；4）产热药物，如选择性β3受体激动剂和选择性甲状腺激素受体β激动剂；5）其他药物，如人生长激素片段（AOD9604）和胃肠道脂肪酶抑制剂（西替利司他）。
