Investigation of the possible antidepressant effects of new thiadiazole derivatives

In this thesis study, based on the activity potentials of 1,3,4-thiadiazole derivatives on the central nervous system, possible antidepressant-like effects of some newly synthesized 1,3,4-thiadiazole derivatives were investigated. In order to examine the antidepressant-like effects of test compounds, tail suspension and modified forced swimming tests were performed. The effects of test compounds on motor coordination of mice were evaluated by Rota-rod tests. In the series, compound 3g shortened the immobility time of mice in tail suspension and modified forced swimming tests. Furthermore, compound 3g increased climbing and swimming times of mice in the modified forced swimming test. These findings indicated that compound 3g had an antidepressant-like effect and this effect might be associated with serotonergic and catecholaminergic neurotransmissions. In the Rota-rod test, unchanged falling latencies of mice from the rotating mill revealed that obtained findings were not related to any change in the motor coordinations of mice. After determining the antidepressant-like effect, p-chlorophenylalanine methyl ester (PCPA), α-methyl-para-tyrosine methyl ester (AMPT) and naloxone were used to elucidate possible mechanisms mediating this effect. PCPA, AMPT and naloxone pretreatments reversed the anti-immobility effect of compound 3g. These findings suggested that the antidepressant-like effect of compound 3g was associated with serotonergic, catecholaminergic and opioidergic mechanisms.