title: Pyrrolidin-2-one derivatives may reduce body weight in rats with diet-induced obesity.
abstract: Obesity affects an increasing number of individuals in the human population and significant importance is attached to research leading to the discovery of drug which would effectively reduce weight. The search for new drugs with anorectic activity and acting within the adrenergic system has attracted the interest of researchers. This study concerns the experimental effects on body weight of α2-adrenoceptor antagonists from the group of pyrrolidin-2-one derivatives in rats with diet-induced obesity.
  
  
  METHODS
  The intrinsic activity of the test compounds at the α-adrenoreceptors was tested. Obesity in rats was obtained by the use of fatty diet and then the influence of the test compounds on body weight, food and water intakes, lipid and glucose profiles and glycerol and cortisol levels were determinated. The effects of the compounds on locomotor activity, body temperature, blood pressure and heart rate were tested.
  
  
  RESULTS
  One of the test compounds (1-(3-(4-phenylpiperazin-1-yl)propyl)pyrrolidin-2-one) reduces the animal's body weight and the amount of peritoneal adipose tissue during chronic administration, at the same time it does not cause significant adverse effects on the cardiovascular system. This compound decreases temperature and elevates glycerol levels and does not change the locomotor activity and cortisol level at anti-obese dose.
  
  
  CONCLUSIONS
  Some derivatives of pyrrolidin-2-one that act as antagonists of the α2-adrenoreceptor may reduce body weight. Reducing body weight for 1-(3-(4-phenylpiperazin-1-yl)propyl)pyrrolidin-2-one can be associated with decrease in food intake, body fat reduction, reduction of blood glucose, and increased thermogenesis and lipolysis. This effect cannot be the result of changes in spontaneous activity or stress.
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University, Collegium Medicum, 9 Medyczna Street, 30-688 Kraków, Poland. Electronic address: magda.dudek@uj.edu.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dudek
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University, Collegium Medicum, 9 Medyczna Street, 30-688 Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Knutelska
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University, Collegium Medicum, 9 Medyczna Street, 30-688 Kraków, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bednarski
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University, Collegium Medicum, 9 Medyczna Street, 30-688 Kraków, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Nowiński
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University, Collegium Medicum, 9 Medyczna Street, 30-688 Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zygmunt
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University, Collegium Medicum, 9 Medyczna Street, 30-688 Kraków, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kazek
authors.affiliation: Department of Pharmacobiology, Jagiellonian University, Collegium Medicum, 9 Medyczna Street, 30-688 Kraków, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Mordyl
authors.affiliation: Department of Pharmacobiology, Jagiellonian University, Collegium Medicum, 9 Medyczna Street, 30-688 Kraków, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Głuch-Lutwin
authors.affiliation: Department of Physicochemical Drug Analysis, Chair of Pharmaceutical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Paula
authors.initials: P
authors.lastname: Zaręba
authors.affiliation: Department of Physicochemical Drug Analysis, Chair of Pharmaceutical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kulig
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University, Collegium Medicum, 9 Medyczna Street, 30-688 Kraków, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects*; D004032:Diet / Q000009:adverse effects*; D005990:Glycerol / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006854:Hydrocortisone / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009765:Obesity / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D011760:Pyrrolidinones / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D022722:Thermogenesis / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D011760:Pyrrolidinones; C028537:2-pyrrolidone; D005990:Glycerol; D006854:Hydrocortisone
keywords: Anti-obesity action; Diet-induced obese rats; Obesity; Pyrrolidin-2-one derivatives; α(2)-Adrenoceptor antagonist