Uthayathas Subramaniam, Karuppagounder Senthilkumar S, Tamer Sibel Ilbasmis, Parameshwaran Kodeeswaran, Degim Tuncer, Suppiramaniam Vishnu, Dhanasekaran Muralikrishnan
Division of Pharmacology and Toxicology, Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.
Life Sci. 2007 Sep 1;81(12):988-92. doi: 10.1016/j.lfs.2007.07.018. Epub 2007 Jul 28.
Sildenafil, a phosphodiesterase-5 inhibitor is widely used for the treatment of erectile dysfunction. Recently, the FDA approved the use of sildenafil in the therapeutic treatment of pulmonary arterial hypertension. Sildenafil crosses the blood-brain barrier and has been shown to enhance memory. Tremor, rigidity and akinesia are the most common symptoms seen in Parkinson's disease. Fatigue and sexual dysfunction are the other prominent features seen in Parkinson's disease. Interestingly, sildenafil is used therapeutically to treat sexual dysfunction in Parkinson's disease patients. Currently research on Parkinson's disease focuses on developing novel drug therapies for retarding the nigral dopaminergic neurodegeneration. Hence, we investigated the anti-fatigue and neuroprotective effects of sildenafil. In this study, the effect of sildenafil on fatigue was evaluated using forced swim test in mice. Sildenafil had no effect on fatigue as seen by the swim time. With regard to neuroprotective effects, we investigated the effects of sildenafil using two animal models of Parkinson's disease. In this study, 6-hydroxydopamine-lesioned (unilateral) rats and MPTP-treated mice were used as the animal models of Parkinson's disease. 6-Hydroxydopamine-lesioned rats were used to determine the effect of sildenafil on rotational behavior. Ipsilateral or contralateral rotational behavior can indicate the amphetamine-like activity or apomorphine-like activity of sildenafil. Sildenafil did not induce contralateral or ipsilateral rotations in 6-hydroxydopamine-lesioned rats. Sildenafil did not protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine depletion in the striatum.
西地那非是一种磷酸二酯酶-5抑制剂，广泛用于治疗勃起功能障碍。最近，美国食品药品监督管理局（FDA）批准将西地那非用于肺动脉高压的治疗。西地那非可穿过血脑屏障，并已被证明能增强记忆力。震颤、僵硬和运动迟缓是帕金森病最常见的症状。疲劳和性功能障碍是帕金森病的其他突出特征。有趣的是，西地那非被用于治疗帕金森病患者的性功能障碍。目前对帕金森病的研究集中在开发延缓黑质多巴胺能神经退行性变的新型药物疗法。因此，我们研究了西地那非的抗疲劳和神经保护作用。在本研究中，使用小鼠强迫游泳试验评估西地那非对疲劳的影响。从游泳时间来看，西地那非对疲劳没有影响。关于神经保护作用，我们使用两种帕金森病动物模型研究了西地那非的作用。在本研究中，6-羟基多巴胺损伤（单侧）大鼠和MPTP处理的小鼠被用作帕金森病动物模型。6-羟基多巴胺损伤的大鼠用于确定西地那非对旋转行为的影响。同侧或对侧旋转行为可表明西地那非的苯丙胺样活性或阿扑吗啡样活性。西地那非在6-羟基多巴胺损伤的大鼠中未诱导对侧或同侧旋转。西地那非不能防止1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的纹状体多巴胺耗竭。
