Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie-Skłodowska University, Lublin, Poland.
Pharmacol Biochem Behav. 2012 Dec;103(2):273-8. doi: 10.1016/j.pbb.2012.08.012. Epub 2012 Aug 25.
Recent studies highlight the involvement of the nitrergic system in the mechanism of action of antidepressant drugs. Sildenafil, a selective PDE5 inhibitor, was shown to abolish the anti-immobility effects of bupropion, venlafaxine and s-citalopram in mice. In this study we assessed the effects of sildenafil on the activity of bupropion and venlafaxine in the forced swim test in mice. Swim trials were conducted by placing mice in glass cylinders filled with water for 6min and the duration of the behavioral immobility during the last 4min of the test was evaluated. Locomotor activity was evaluated with photoresistor actimeters. Brain and serum concentrations of the studied antidepressants were determined by HPLC method. Sildenafil at a dose of 20mg/kg, but not 5 and 10mg/kg, significantly increased the anti-immobility action of bupropion (20mg/kg). The antidepressant activity of venlafaxine (2mg/kg) was potentiated by joint administration with sildenafil at doses of 10 and 20mg/kg. Since the combined treatments did not increase the locomotor activity, the antidepressant-like effects were not related to non-specific behavioral activation. Data from pharmacokinetic studies revealed that sildenafil increased bupropion and venlafaxine levels in serum without affecting their concentrations in the brain. The present study demonstrates the enhancement of anti-immobility action of bupropion and venlafaxine by sildenafil co-administration. The observed changes might have been partly due to pharmacokinetic interactions. However, mechanisms underlying the effects of sildenafil on the antidepressant activity of bupropion and venlafaxine should be carefully evaluated in further studies.
最近的研究强调了氮能系统在抗抑郁药作用机制中的参与。西地那非是一种选择性 PDE5 抑制剂，它被证明可以消除丁胺苯丙酮、文拉法辛和西酞普兰在小鼠中的抗不动作用。在这项研究中，我们评估了西地那非对丁胺苯丙酮和文拉法辛在小鼠强迫游泳试验中的活性的影响。游泳试验通过将小鼠放入装满水的玻璃圆柱中进行 6 分钟，并评估试验最后 4 分钟内行为不动的持续时间。运动活动通过光电电阻活动计进行评估。通过 HPLC 方法测定研究抗抑郁药在大脑和血清中的浓度。西地那非剂量为 20mg/kg，但 5mg/kg 和 10mg/kg 剂量不会显著增加丁胺苯丙酮（20mg/kg）的抗不动作用。文拉法辛（2mg/kg）的抗抑郁活性在与西地那非（10mg/kg 和 20mg/kg）联合给药时增强。由于联合治疗并未增加运动活动，因此抗抑郁样作用与非特异性行为激活无关。药代动力学研究的数据表明，西地那非增加了丁胺苯丙酮和文拉法辛在血清中的水平，而不影响其在大脑中的浓度。本研究表明，西地那非联合给药增强了丁胺苯丙酮和文拉法辛的抗不动作用。观察到的变化可能部分归因于药代动力学相互作用。然而，在进一步的研究中应仔细评估西地那非对丁胺苯丙酮和文拉法辛抗抑郁活性的影响的机制。
