Depression-like Effect of Losartan Potassium on Immobility in Mice: Preliminary Evidence for the Involvement of Its Active Metabolite Exp 3174

The effect of acute oral treatment of losartan potassium, an angiotensin AT1 receptor blocker, on immobility in the forced swim test have been studied using rifampicin-treated (cytochrome P-450 enzyme-induced) and fluconazole-treated (cytochrome P-450 enzyme-inhibited) swiss albino mice respectively. In vehicle-treated group, an enhancement in immobility time was observed at 3 h and 6 h after losartan potassium treatment (20 mg/kg, p.o) in the mouse forced swim test. In rifampicin-treated group, even at 1 h after losartan potassium treatment (20 mg/kg, p.o.) a significant enhancement in immobility was observed. It has also been observed that the basal immobility time of rifampicin-treated mice was significantly (p<0.001) lower when compared with vehicle treated group. In fluconazole-treated group, losartan potassium (20 mg/kg, p.o.) could not significantly alter the immobility time at any point of time. The present study results suggest that the depression-like effect of losartan potassium might be mainly mediated by its active metabolite EXP 3174. However, further studies using EXP 3174 are warranted to confirm its CNS activities.