Neuroscience Department, University of Parma, Italy; Department of Clinical and Experimental Medicine, Unity of Andrological Medicine, University of Parma, Italy.
Behav Brain Res. 2013 Sep 15;253:103-12. doi: 10.1016/j.bbr.2013.07.004. Epub 2013 Jul 11.
Selective phosphodiesterases (PDEs) inhibitors have been widely studied as therapeutic agents for treatment of various human diseases, including cardiotonics, vasodilators, smooth muscle relaxants, antidepressants, antithrombotics, antiasthmatics, and agents for improving learning and memory. Although Sildenafil(®) and Vardenafil(®) have similar chemical formulae, the same target and interact with many of the same residues at the active site of phosphodiesterse-5 (PDE-5), they exhibit both in vitro and in vivo some important functional differences that could differentially affect behavior. Therefore we assessed whether repeated and chronic administration of Vardenafil and Sildenafil at a dose based upon human treatment can differentially affect aggressive, social, emotional and sexual behavior. To this aim, the effects of Sildenafil (10mg/kg) or Vardenafil (2mg/kg) (t.i.w., for 5 weeks) were observed in CD1 subordinate male mice in a low aggression and social subordination context. The results show that Sildenafil increased competitive aggression, environmental and social exploration, and reduced anxiety like behaviors as compared to controls, whereas Vardenafil had a significant major effect on appetitive and consummatory aspect of sexual behavior. This demonstrates that Sildenafil and Vardenafil, although being structurally and functionally similar, are characterized by different neuro-behavioral actions and can have differential therapeutic potentials.
选择性磷酸二酯酶（PDE）抑制剂已被广泛研究作为治疗各种人类疾病的治疗剂，包括强心剂、血管扩张剂、平滑肌松弛剂、抗抑郁药、抗血栓药、抗哮喘药和改善学习和记忆的药物。尽管西地那非（Sildenafil(®)）和伐地那非（Vardenafil(®)）具有相似的化学公式，相同的靶标，并与磷酸二酯酶-5（PDE-5）的活性位点的许多相同残基相互作用，但它们在体外和体内表现出一些重要的功能差异，这些差异可能会对行为产生不同的影响。因此，我们评估了以基于人类治疗的剂量重复和慢性给予伐地那非和西地那非是否会对攻击性行为、社交行为、情绪和性行为产生不同的影响。为此，我们观察了西地那非（10mg/kg）或伐地那非（2mg/kg）（每天一次，连续 5 周）在低攻击性和社会从属环境下对 CD1 从属雄性小鼠的影响。结果表明，与对照组相比，西地那非增加了竞争性攻击行为、环境和社会探索行为，并减少了焦虑样行为，而伐地那非对性行为的食欲和满足方面有显著的主要影响。这表明，西地那非和伐地那非虽然在结构和功能上相似，但具有不同的神经行为作用，并具有不同的治疗潜力。
