The pharmacological profile of pitolisant, a histamine H3 receptor 
antagonist/inverse agonist, indicates that this compound might reduce body 
weight and metabolic disturbances. Therefore, we studied the influence of 
pitolisant on body weight, water and sucrose intake as well as metabolic 
disturbances in the high-fat and high-sugar diet-induced obesity model in mice. 
To induce obesity, male CD-1 mice were fed a high-fat diet consisting of 40% fat 
blend for 14 weeks, water and 30% sucrose solution available ad libitum. Glucose 
tolerance test was performed at the beginning of week 15. Insulin tolerance was 
tested the day after. At the end of study, plasma levels of triglycerides and 
cholesterol were determined. Pitolisant at dose of 10 mg/kg bw (ip) was 
administrated during 14 days, starting from the beginning of week 13. Metformin 
at dose of 100 mg/kg bw (ip) was used as reference drug. Mice fed with high-fat 
diet and sucrose solution showed more weight gain throughout the 12-week period 
of inducing obesity. Animals fed with high-fat diet and treated with pitolisant 
(for the next 14 days) showed significantly less weight gain than mice from the 
control group consuming a high-fat feed. In the group treated with pitolisant, 
glucose levels were significantly lower than glucose levels of control obese 
mice after glucose load. The plasma triglyceride levels in pitolisant-treated 
mice were significantly lower compared with those in control obese group. In 
conclusion, pitolisant has a favorable influence of body weight and improves 
glucose tolerance and the lipid profile in obese mice.