Abstract
Creating of new antidepressants is actual problem in the modern society, because of increase of the amount of people with depression. According to WHO, about 4-5% of the world's population suffers from depression. About 15% of patients with depression commit suicide; among all suicides in 60% of incidents their cause is depression.
We conducted a research of the 5 new thietan-phenol thiazolium bromide's derivates' (L-512, L-521, L-524, L-525, L-526) psychotropic activity in mice behavioral tests: tail suspention test (TST), forced swimming test (FST), elevated plus maze test (EPMT) and open field test (OFT).
Two series of experiments were carried out. The substances were injected intraperitoneally for 14 days and once a day 30 minutes before tests.
There were administrations of NaCl, Fluoxetinum and Diazepamum in the control groups. We also determined the toxity by acute toxity test and OSIRIS Property Explorer. Statistical treatment was made in program «Statistica 10.0»: we used mediana, quartile; Mann-Whithey U-test and Kruskal-Wallis test for comparing.
After single injection in FST L-524 significantly increased the immobility time by 88% (comparatively to the control group) and depression index had been redused by 41%. In TST duration of immobilization decreased by 26%. We detected an increase of orientation and exploration activity by 50% and horizontal activity by 55% in OFT. After subchronical administration L-512 decreased the depression index by 36% and immobility time by 32% in FST. In TST L-512 decreased the immobility time by 52%. It also decreased orientation and exploration activity and horizontal activity in OFT.
All molecules correspond to Lipinsky's "Rule of Five." Presumably synthesized molecules do not have mutagenic, tumorigenic properties and do not have a toxic effect on the reproductive system. LD-50 is around 100-1000 mg/ml.
In brief, new thietan-phenol thiazolium bromide's derivates are low-toxic and can become medicines. Experiments on mice have given proof of antidepressant-like activity of compounds L-524 and L-512. They are the most perspective for the further study and research of molecules with psychotropic activity.
