The novel antiobesic HMR1426 reduces food intake without affecting energy expenditure in rats.
OBJECTIVE
To determine the effect of acute and chronic administration of a new food intake-reducing compound (HMR1426) with novel mode of action (retardation of gastric emptying) on body weight development, food intake, and energy metabolism in rats.


METHODS
Adult male Shoe-Wistar rats were implanted with transponders allowing registration of body temperature (Tb) and locomotor activity. HMR1426 (10 or 50 mg/kg) was given orally, and acute (8 hours) and chronic (15 days) effects were measured on food intake, Tb, activity, total energy expenditure (indirect calorimetry), and epididymal adipose tissue mass. The effect of chronic treatment was compared with the effect of sibutramine (10 mg/kg).


RESULTS
HMR1426 (50 mg/kg) caused an acute and chronic decrease of food intake. There was no effect on the level and daily pattern of total energy expenditure, Tb, and locomotor activity. Respiratory quotient was acutely decreased by HMR1426 due to reduced food intake. Chronic treatment with HMR1426 decreased weight gain by 31% and epididymal white fat by 24%. Sibutramine caused a respective reduction of 48% and 35%. Energy efficiency was not affected by HMR1426 in contrast to sibutramine, which reduced energy efficiency and transiently increased activity.


CONCLUSIONS
HMR1426 showed an anorectic potential in rats and decreased body weight and fat mass. This was achieved solely by reducing food intake without influencing overall energy expenditure or behavior suggesting a peripheral mode of action. Thus, HMR1426 can be considered a potential new drug for obesity treatment.
Ortmann
Sylvia
S
Group of Energy Metabolism, German Institute of Human Nutrition in Potsdam, Nuthetal, Germany.
Kampe
Juliane
J
Gossel
Matthias
M
Bickel
Martin
M
Geisen
Karl
K
Jähne
Gerhard
G
Lang
Hans Jochen
HJ
Klaus
Susanne
S
D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D003503:Cyclobutanes / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D015430:Weight Gain / Q000187:drug effects
D019440:Anti-Obesity Agents; D003503:Cyclobutanes; C483460:HMR 1426; D006575:Heterocyclic Compounds, 3-Ring; C058254:sibutramine