Study of antidepressive activity and safety profile of new thietan-1, 1-dioxyde derivatives

Antidepressive properties and safety profile of three new thietan-1,1-dioxide derivatives (N14, N40, N69) have been studied on male mice. Antidepressive effects were studied in the forced swimming test. It has been shown that all compounds (2 mg/kg, i.p.) significantly reduced immobility time (by 30-50%) and depression index (by 26-38%) in a single administration, and at 14-day administration - depression index alone (by 48-51%). The antidepressant-like effect of the compounds was comparable with that of fluoxetine (10 mg/kg). The substances did not modify the animals' behavior in the open field test. The LD(50) values for intraperitoneal administration in male mice for the N14, N40, N69 were 504, 1100 and 148 mg/kg, respectively, and therapeutic index of the compounds exceeded that of fluoxetine 9.3, 13.6 and 1.7 times, respectively.