title: Idalopirdine - a small molecule antagonist of 5-HT6 with therapeutic potential against obesity.
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.
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University, Collegium Medicum, 9 Medyczna Street, PL 30-688, Kraków, Poland. magda.dudek@uj.edu.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dudek
authors.affiliation: Chair of Pharmaceutical Chemistry, Faculty of Pharmacy, Jagiellonian University, Collegium Medicum, Medyczna 9, 30-688, Kraków, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Marcinkowska
authors.affiliation: Chair of Pharmaceutical Chemistry, Faculty of Pharmacy, Jagiellonian University, Collegium Medicum, Medyczna 9, 30-688, Kraków, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Bucki
authors.affiliation: Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Olczyk
authors.affiliation: Chair of Pharmaceutical Chemistry, Faculty of Pharmacy, Jagiellonian University, Collegium Medicum, Medyczna 9, 30-688, Kraków, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kołaczkowski
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000821:Animal Feed / Q000032:analysis; D000818:Animals; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D001067:Appetite Depressants / Q000627:therapeutic use*; D001596:Benzylamines / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D007211:Indoles / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009765:Obesity / Q000188:drug therapy*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D005466:Fluorocarbons
chemical_list: D019440:Anti-Obesity Agents; D001067:Appetite Depressants; D001596:Benzylamines; D001786:Blood Glucose; D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C568612:(2-(6-fluoro-1H-indol-3-yl)-ethyl)-(3-(2,2,3,3-tetrafluoropropoxy)benzyl)amine; D005466:Fluorocarbons; C097216:serotonin 6 receptor
keywords: 5-HT6 receptor antagonist; Anorectic activity; Idalopirdine; LuAE58054; Obesity; Rats with diet-induced obesity