Socała Katarzyna, Nieoczym Dorota, Wyska Elżbieta, Wlaź Piotr
Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, PL-20033, Lublin, Poland.
Department of Pharmacokinetics and Physical Pharmacy, Collegium Medicum, Jagiellonian University, Kraków, Poland.
Naunyn Schmiedebergs Arch Pharmacol. 2017 Apr;390(4):339-349. doi: 10.1007/s00210-016-1334-3. Epub 2016 Dec 24.
Sildenafil, a potent and selective inhibitor of phosphodiesterase type 5, is used clinically to treat erectile dysfunction and pulmonary arterial hypertension. It is often taken by patients suffering from depression and receiving antidepressant drug treatment. However, its influence on the efficacy of antidepressant treatment was not sufficiently studied. Therefore, the aim of the present study was to investigate the influence of sildenafil on the anti-immobility action of several antidepressant drugs (i.e., sertraline, fluvoxamine, citalopram, maprotiline, trazodone, and agomelatine) as well as on antidepressant-like effect of electroconvulsive stimulations in the forced swim test in mice. The obtained results showed that acute sildenafil treatment enhanced the antidepressant-like activity of all of the studied drugs. The observed effects were not due to the increase in locomotor activity. The interactions between sildenafil and sertraline, maprotiline, and trazodone were pharmacodynamic in nature, as sildenafil did not affect concentrations of these drugs neither in serum nor in brain tissue. Increased concentrations of fluvoxamine, citalopram, and agomelatine in brain tissue evoked by sildenafil co-administration suggest that pharmacokinetic interactions between sildenafil and these drugs are very likely. Sildenafil injected acutely did not alter the antidepressant-like efficacy of electroconvulsive stimulations in mice, as assessed in the forced swim test. Interestingly, repeated (14 days) administration of sildenafil decreased the anti-immobility action of the electroconvulsive stimulations. In conclusion, the present study shows that sildenafil may alter the effectiveness of antidepressant treatment. Further studies are warranted to better characterize the influence of sildenafil on the activity of antidepressant drugs and electroconvulsive therapy.
西地那非是一种强效且选择性的5型磷酸二酯酶抑制剂，临床上用于治疗勃起功能障碍和肺动脉高压。患有抑郁症并接受抗抑郁药物治疗的患者经常服用该药。然而，其对抗抑郁治疗疗效的影响尚未得到充分研究。因此，本研究的目的是探讨西地那非对几种抗抑郁药物（即舍曲林、氟伏沙明、西酞普兰、马普替林、曲唑酮和阿戈美拉汀）抗不动作用的影响，以及对小鼠强迫游泳试验中电惊厥刺激的抗抑郁样效应的影响。所得结果表明，西地那非急性治疗增强了所有研究药物的抗抑郁样活性。观察到的效应并非由于运动活性增加所致。西地那非与舍曲林、马普替林和曲唑酮之间的相互作用本质上是药效学的，因为西地那非既不影响这些药物在血清中也不影响在脑组织中的浓度。西地那非联合给药引起脑组织中氟伏沙明、西酞普兰和阿戈美拉汀浓度升高，提示西地那非与这些药物之间很可能存在药代动力学相互作用。在强迫游泳试验中评估，急性注射西地那非不会改变小鼠电惊厥刺激的抗抑郁样疗效。有趣的是，重复（14天）给予西地那非会降低电惊厥刺激的抗不动作用。总之，本研究表明西地那非可能会改变抗抑郁治疗的效果。有必要进一步研究以更好地表征西地那非对抗抑郁药物活性和电惊厥治疗的影响。
