Dudek Magdalena, Marcinkowska Monika, Bucki Adam, Olczyk Adrian, Kołaczkowski Marcin
Department of Pharmacodynamics, Jagiellonian University, Collegium Medicum, 9 Medyczna Street, PL 30-688, Kraków, Poland.
Chair of Pharmaceutical Chemistry, Faculty of Pharmacy, Jagiellonian University, Collegium Medicum, Medyczna 9, 30-688, Kraków, Poland.
Metab Brain Dis. 2015 Dec;30(6):1487-94. doi: 10.1007/s11011-015-9736-3. Epub 2015 Sep 29.
5HT6 receptor antagonists offer the potential for safe and effective drugs against obesity, because they can reduce weight without causing serious side effects in the cardiovascular system. Also, their anorexic effect is associated with reduced food intake via an enhancement of satiety. In the present study we investigated the anorexic effect of idalopirdine (LuAE58054) in a model of obesity induced by high-fat diet. To induce obesity in rats, the animals were treated with feed with a fat content of 40 %. Body weight was controlled and the amount of food and water consumed was determined. The influence of the test compound on the lipid profile and glucose level was measured, as well as locomotor activity in home cages on the 20th day of the treatment. LuAE58054, at 5 mg kg(-1)/day i.p., was significantly anorectic in this model of obesity. Animals treated with LuAE58054 weighed 8 and 9.2 % less than the control obese animals on the 12th and 21st days, respectively. It significantly reduced food intake and the amount of peritoneal fat in animals, and reduced the level of triglycerides in plasma. LuAE58054 did not have a statistically significant effect on the spontaneous activity of diet-induced obese rats. The present study clearly demonstrates the effectiveness of LuAE58054 in reducing body weight. This compound is in phase III of clinical trials for the treatment of cognitive deficits associated with Alzheimer's disease and schizophrenia. It is a 5HT6 receptor antagonist and is, therefore, free of those unacceptable side effects that preclude chronic use of anti-obesity drugs with other mechanisms of action. The search for an effective and safe anti-obesity drug is essential for an increasingly obese population; therefore, the anorectic action of LuAE58054 is important and there is a need for more research in this direction.
5-羟色胺6（5HT6）受体拮抗剂为研发安全有效的抗肥胖药物提供了可能，因为它们能够减轻体重，同时不会在心血管系统中引发严重的副作用。此外，它们的厌食作用与通过增强饱腹感来减少食物摄入量有关。在本研究中，我们在高脂饮食诱导的肥胖模型中研究了依达哌啶（LuAE58054）的厌食作用。为了诱导大鼠肥胖，给动物喂食脂肪含量为40%的饲料。控制体重，并测定食物和水的消耗量。测量受试化合物对脂质谱和血糖水平的影响，以及在治疗第20天动物在饲养笼中的自发活动。在该肥胖模型中，腹腔注射给予5mg/kg/天的LuAE58054具有显著的厌食作用。在第12天和第21天，用LuAE58054治疗的动物体重分别比对照肥胖动物轻8%和9.2%。它显著减少了动物的食物摄入量和腹膜脂肪量，并降低了血浆甘油三酯水平。LuAE58054对饮食诱导的肥胖大鼠的自发活动没有统计学上的显著影响。本研究清楚地证明了LuAE58054在减轻体重方面的有效性。该化合物正处于治疗与阿尔茨海默病和精神分裂症相关的认知缺陷的临床试验III期。它是一种5HT6受体拮抗剂，因此没有那些会妨碍长期使用具有其他作用机制的抗肥胖药物的不可接受的副作用。对于日益肥胖的人群来说，寻找一种有效且安全的抗肥胖药物至关重要；因此，LuAE58054的厌食作用很重要，并且需要在这个方向上进行更多的研究。
