In an effort to develop potent antidepressant agents, new pyrazoline derivatives 2a–s were synthesized and evaluated for their antidepressant-like activity by tail suspension test (TST) and modified forced swimming test (MFST). The effects of the compounds on spontaneous locomotor activity were also investigated using an activity cage apparatus. Among these derivatives, compounds 2b, 2d, 2f, 2o, and 2r decreased both horizontal and vertical activity number of the mice. On the other hand, compounds 2a, 2h, 2j, 2k, 2l, 2m, and 2n, which did not induce any significant change in the locomotor activity, significantly shortened the immobility time of mice in TST and MFST, representing the presence of the antidepressant-like effect. Additionally, the same compounds increased the swimming time of mice in MFST without any change in climbing duration, similar to the reference drug fluoxetine (10 mg/kg). In the light of previous papers examining the effects of pyrazolines on central nervous system, this study, once more, pointed out remarkable antidepressant activity potential of pyrazoline derivatives.

Within the scope of our new antidepressant drug development efforts, in this study, we synthesized eight novel benzothiazole derivatives 3a–3h. The chemical structures of the synthesized compounds were elucidated by spectroscopic methods. Test compounds were administered orally at a dose of 40 mg/kg to mice 24, 5 and 1 h before performing tail suspension, modified forced swimming, and activity cage tests. The obtained results showed that compounds 3c, 3d, 3f–3h reduced the immobility time of mice as assessed in the tail suspension test. Moreover, in the modified forced swimming tests, the same compounds significantly decreased the immobility, but increased the swimming frequencies of mice, without any alteration in the climbing frequencies. These results, similar to the results induced by the reference drug fluoxetine (20 mg/kg, po), indicated the antidepressant-like activities of the compounds 3c, 3d, 3f–3h. Owing to the fact that test compounds did not induce any significant alteration in the total number of spontaneous locomotor activities, the antidepressant-like effects of these derivatives seemed to be specific. In order to predict ADME parameters of the synthesized compounds 3a–3h, some physicochemical parameters were calculated. The ADME prediction study revealed that all synthesized compounds may possess good pharmacokinetic profiles.

Novel thiadiazole derivatives were synthesized through the reaction of acetylated 2-aminothiadiazole and piperazine derivatives. The chemical structures of the compounds were clarified by Infrared Spectroscopy (IR), ¹H Nuclear Magnetic Resonance Spectroscopy (¹H-NMR), ¹³C Nuclear Magnetic Resonance Spectroscopy (¹³C-NMR) and Electronspray Ionisation Mass Spectroscopy (ESI-MS) spectroscopic methods. Antidepressant-like activities were evaluated by the tail-suspension (TST) and modified forced swimming (MFST) methods. Besides, possible influence of the test compounds on motor activities of the animals were examined by activity cage tests. In the TST, administration of the compounds 2c, 2d, 2e, 2f, 2g and 2h significantly decreased the immobility time of mice regarding the control values. Further, in the MFST, the same compounds reduced the total number of immobility behaviors while increasing swimming performance. However, no change was observed in the total number of climbing behaviors. These data suggested that compounds 2c, 2d, 2e, 2f, 2g and 2h possess notable antidepressant-like activities. Reference drug fluoxetine (10 mg/kg) was also exhibited its antidepressant activity, as expected. No significant difference was seen between the locomotor activity values of the test groups signifying that observed antidepressant-like activities are specific. Theoretical calculation of absorption, distribution, metabolism, excretion (ADME) properties for the obtained compounds were performed and obtained data supported the antidepressant-like potential of these novel thiadiazole derivatives.

The aim of this work was to investigate the effects of St. John's Wort (SJW) extract treatment on behavioral changes arising in streptozotocin (STZ)-diabetic rats. Plus-maze, activity cage, modified forced swimming, and active avoidance tests were performed for evaluating exploratory behaviors, spontaneous locomotor activities, depression levels, and learning parameters of animals, respectively. Obtained data exhibited a diabetes mellitus (DM)-induced increase in anxiety and depression levels, decrease in spontaneous locomotor activities, and impairment of learning parameters in rats even in the early stages of the disease. Daily insulin replacement (2 IU/kg/day) could not restore these impaired parameters completely, indicating the need of novel therapeutic approaches. SJW extract (125 and 250 mg/kg) treatments for seven days provided significant improvement in all of the impaired parameters observed in this study, probably due to its antidiabetic and central nervous system (CNS)-related effects. Based on the findings of the present study, it may be suggested that SJW extracts may be of help to diabetic patients suffering from depressive moods, sleeping disturbances, and cognitive deficits and may provide a new potential alternative for the treatment of psychiatric complications of diabetes.