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Idalopirdine – a small molecule antagonist of 5-HT(6) with therapeutic potential against obesity

5HT(6) 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 pre...

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Autores principales: Dudek, Magdalena, Marcinkowska, Monika, Bucki, Adam, Olczyk, Adrian, Kołaczkowski, Marcin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642593/
https://www.ncbi.nlm.nih.gov/pubmed/26419385
http://dx.doi.org/10.1007/s11011-015-9736-3
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author Dudek, Magdalena
Marcinkowska, Monika
Bucki, Adam
Olczyk, Adrian
Kołaczkowski, Marcin
author_facet Dudek, Magdalena
Marcinkowska, Monika
Bucki, Adam
Olczyk, Adrian
Kołaczkowski, Marcin
author_sort Dudek, Magdalena
collection PubMed
description 5HT(6) 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 5HT(6) 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.
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spelling pubmed-46425932015-11-17 Idalopirdine – a small molecule antagonist of 5-HT(6) with therapeutic potential against obesity Dudek, Magdalena Marcinkowska, Monika Bucki, Adam Olczyk, Adrian Kołaczkowski, Marcin Metab Brain Dis Original Article 5HT(6) 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 5HT(6) 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. Springer US 2015-09-29 2015 /pmc/articles/PMC4642593/ /pubmed/26419385 http://dx.doi.org/10.1007/s11011-015-9736-3 Text en © The Author(s) 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Dudek, Magdalena
Marcinkowska, Monika
Bucki, Adam
Olczyk, Adrian
Kołaczkowski, Marcin
Idalopirdine – a small molecule antagonist of 5-HT(6) with therapeutic potential against obesity
title Idalopirdine – a small molecule antagonist of 5-HT(6) with therapeutic potential against obesity
title_full Idalopirdine – a small molecule antagonist of 5-HT(6) with therapeutic potential against obesity
title_fullStr Idalopirdine – a small molecule antagonist of 5-HT(6) with therapeutic potential against obesity
title_full_unstemmed Idalopirdine – a small molecule antagonist of 5-HT(6) with therapeutic potential against obesity
title_short Idalopirdine – a small molecule antagonist of 5-HT(6) with therapeutic potential against obesity
title_sort idalopirdine – a small molecule antagonist of 5-ht(6) with therapeutic potential against obesity
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642593/
https://www.ncbi.nlm.nih.gov/pubmed/26419385
http://dx.doi.org/10.1007/s11011-015-9736-3
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