H2-receptor antagonist reduces food intake and weight gain in rats by non-gastric acid secretory mechanisms

ABSTRACT

The H₂-receptor antagonist cimetidine reduces appetite and weight in overweight healthy subjects and in overweight subjects with type II diabetes mellitus. The aim of this study was to characterize the mechanisms of this effect in rodents. Drugs were administered three times a day, 30 min before 1 h periods of free access to food. In one group of rats (n=9), cimetidine (8 mg) treatment resulted in significantly lower cumulative food intake than in a control group (n=9). The total intakes of food during the observation period of 22 days were 325.3 ± 29.1 g and 346.3 ± 16.7 g in the cimetidine and control groups, respectively. During the observation period, the weight gain in the cimetidine group was 63.3 ± 15.8 g, which was significantly lower than the weight gain of 74.8 ± 14.2 g in the control group, i.e. the cimetidine induced a 15.4% reduction in the weight gain during the observation period of 22 days. The weight gained per weight of food ingested was 0.20 ± 0.04 (g/g) and 0.22 ± 0.04 (g/g) in the cimetidine and control groups, respectively (NS). In other experiments, ranitidine (3 mg) and famotidine (0.4 mg), but not omeprazole (0.4 mg), taken three times a day for 8 days reduced the weight gain when compared with a control group (n=7 in each group). We therefore conclude that the effects of the H₂-receptor antagonists are not mediated by inhibitory mechanisms on the gastric acid secretion.