ABSTRACT
Background: Cardiovascular diseases are commonly associated with depression. Calcium channel blockers (CCBs) form commonly used group of drugs for the treatment of a number of cardiovascular diseases. Nifedipine, a CCB, has been shown to possess antidepressant activity and potentiate antidepressant activity of imipramine and sertraline, however, literature on its interaction with newer antidepressant drugs such as fl uvoxamine, venlafaxine and tianeptine is limited. Hence, the present study was undertaken. Methods: The study was carried out in albino mice in two phases. In Phase I, antidepressant activity of nifedipine, fl uvoxamine, venlafaxine and tianeptine were confi rmed after their single dose administration using forced swim test (FST) and tail suspension test (TST) and their minimum antidepressant doses were determined. In Phase II, the effect of nifedipine on antidepressant activity of fl uvoxamine, venlafaxine and tianeptine was studied by orally administering sub-antidepressant doses of these drugs for 28 days. FST and TST were carried out on 1st, 14th and 28th day of the study and change in immobility period was observed. Results: In Phase I, all the studied drugs exhibited dose dependent antidepressant activity in both FST and TST. Minimal antidepressant dose of nifedipine, fl uvoxamine, venlafaxine and tianeptine was observed as 10, 25, 25 and 10 mg/kg respectively. In Phase II, combinations of sub-antidepressant dose of nifedipine (5 mg/kg) with sub-antidepressant doses of fl uvoxamine (12.5 mg/kg), venlafaxine (12.5 mg/kg) and tianeptine (5 mg/kg) exhibited enhanced antidepressant activity when compared to the control group and individual drug groups after same duration of treatment. Conclusions: Nifedipine, fluvoxamine, venlafaxine and tianeptine possess antidepressant activity and nifedipine exhibits synergistic antidepressant activity with fl uvoxamine, venlafaxine and tianeptine.
ABSTRACT
Background: Paracetamol is used for symptomatic treatment of fever and pain with isoniazid and other anti-tubercular drugs in patients of tuberculosis. Literature has conflicting data regarding their interaction. Some studies show that isoniazid increases oxidative metabolism of paracetamol whereas some other suggest that isoniazid has an inhibitory effect. The present study was conducted to find out the possible interaction between paracetamol and isoniazid. Methods: The study was undertaken on Wistar strain of Albino rats. Group I and Group II animals were treated with paracetamol (500 mg/kg) and the combination of paracetamol (500 mg/kg) and isoniazid (30 mg/kg) respectively for 2 months. Blood samples were taken before and during the study for biochemical and histopathological studies of liver and renal functions and plasma paracetamol concentration was also evaluated. Results: Isoniazid decreased the plasma paracetamol concentration without affecting its analgesic activity. However, the hepatotoxic and nephrotoxic effects of paracetamol were found to be further aggravated by isoniazid co-administration. Conclusion: Isoniazid potentiates the hepatotoxic and nephrotoxic effects of paracetamol possibly due to hepatic enzyme induction by isoniazid.