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Idalopirdine - a small molecule antagonist of 5-HT6 with therapeutic potential against obesity.

Dudek M, Marcinkowska M, Bucki A, Olczyk A, Kołaczkowski M - Metab Brain Dis (2015)

Bottom Line: 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.The present study clearly demonstrates the effectiveness of LuAE58054 in reducing body weight.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacodynamics, Jagiellonian University, Collegium Medicum, 9 Medyczna Street, PL 30-688, Kraków, Poland. magda.dudek@uj.edu.pl.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Locomotor Activity during 24 h after treatment with LuAE58054 or vehicle to DIO rats on 20th day of treatment. Activity is directly related to entering various areas of the cage (a) and inversely related to time spent in particular areas of the cage (b). Results are means, n = 6
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Fig4: Locomotor Activity during 24 h after treatment with LuAE58054 or vehicle to DIO rats on 20th day of treatment. Activity is directly related to entering various areas of the cage (a) and inversely related to time spent in particular areas of the cage (b). Results are means, n = 6

Mentions: In the group treated with the tested compound – Lu AE58054 – no statistically significant effect on the spontaneous activity of DIO rats was observed in comparison with the DIO-control group. Figure 4 shows the results.Fig 4


Idalopirdine - a small molecule antagonist of 5-HT6 with therapeutic potential against obesity.

Dudek M, Marcinkowska M, Bucki A, Olczyk A, Kołaczkowski M - Metab Brain Dis (2015)

Locomotor Activity during 24 h after treatment with LuAE58054 or vehicle to DIO rats on 20th day of treatment. Activity is directly related to entering various areas of the cage (a) and inversely related to time spent in particular areas of the cage (b). Results are means, n = 6
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4642593&req=5

Fig4: Locomotor Activity during 24 h after treatment with LuAE58054 or vehicle to DIO rats on 20th day of treatment. Activity is directly related to entering various areas of the cage (a) and inversely related to time spent in particular areas of the cage (b). Results are means, n = 6
Mentions: In the group treated with the tested compound – Lu AE58054 – no statistically significant effect on the spontaneous activity of DIO rats was observed in comparison with the DIO-control group. Figure 4 shows the results.Fig 4

Bottom Line: 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.The present study clearly demonstrates the effectiveness of LuAE58054 in reducing body weight.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacodynamics, Jagiellonian University, Collegium Medicum, 9 Medyczna Street, PL 30-688, Kraków, Poland. magda.dudek@uj.edu.pl.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus