Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Evaluation of neuroprotective and anti-fatigue effects of sildenafil. 1782 48

Anagrelide is a phosphodiesterase III inhibitor utilized in the treatment of essential thrombocythemia. Anagrelide can be responsible for positive inotropic and chonotropic activity of the cardiovascular system. Moreover, it can induce vasospam directly on the epicardial coronary arteries. In the literature, it is well reported that this inhibitor can determine serious cardiovascular side effects, including congestive heart failure, arrhythmia and acute coronary syndrome. We describe the case of a 75-year-old woman who developed a mid-ventricular Takotsubo syndrome while on anagrelide therapy. Takotsubo cardiomyopathy, also known as left ventricular ballooning syndrome, is characterized by a reversible ventricular contractile dysfunction with akinesis and expansion of apical segments and hyperkinesis of the basal segments. Recently, atypical cases with akinesia and dilation of mid-ventricular segment and hypercontraction of the apical segments, also called mid-ventricular and inverted Takotsubo syndrome, have been described. Even though the pathogenesis of Takotsubo syndrome is poorly understood, several mechanisms have been proposed, including catecholamine-induced myocardial stunning, and ischemia-mediated stunning due to multivessel epicardial or microvascular spasm. We think that in our case, the adverse response of anagrelide therapy was determined, by accumulated dosage of the drug, through an intensive inotropic stimulation and a sympathetic hyperactivation in a vulnerable myocardium. To our knowledge, this is one of the first reports of an association between anagrelide therapy and Takotsubo cardiomyopathy.
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PMID:Atypical Takotsubo syndrome during anagrelide therapy. 1939 76