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

Sildenafil citrate (Viagra) is a potent and specific inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), which exhibits cardioprotective action against ischemia/reperfusion injury in intact and isolated heart. The mechanism of its cardioprotective action is not completely understood, but some results suggested that sildenafil exerts cardioprotection through the opening of mitochondrial ATP-sensitive K+ channels (mitoKATP). However, the impact of sildenafil citrate per se on isolated heart mitochondrial function is unknown. The goal of this study was to investigate the influence of the compound on mitochondrial function (bioenergetics, Ca2+-induced mitochondrial permeability transition, and hydrogen peroxide (H2O2) generation) in an attempt to correlate its known actions with effects on heart mitochondria. It was observed that sildenafil citrate concentrations of up to 50 muM did not significantly affect glutamate/malate-supported respiration in states 2, 3, 4, oligomycin-inhibited state 3, and uncoupled respiration. The respiratory control ratio (RCR), the ADP to oxygen ratio (ADP/O), the transmembrane potential (DeltaPsi), the phosphorylation rate, and the membrane permeability to H+, K+ and Ca2+ were not affected either. However, sildenafil citrate decreased H2O2 generation by mitochondria respiring glutamate/malate, and also decreased the formation of superoxide radical (O2 (*-) ) generated in a hypoxantine/xantine oxidase system. It was concluded that sildenafil citrate concentrations of up to 50 microM do not affect either rat heart mitochondrial bioenergetics or Ca2+-induced mitochondrial permeability transition, but it depresses H2O2 generation by acting as a superoxide dismutase (SOD)-mimetic. By preventing reactive oxygen species (ROS) generation, sildenafil citrate may preserve heart mitochondrial function.
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PMID:Sildenafil citrate concentrations not affecting oxidative phosphorylation depress H2O2 generation by rat heart mitochondria. 1802 20

Although sildenafil (Viagra) and other phosphodiesterase V (PDE V) inhibitors are increasingly recognized for their use in the treatment of male erectile dysfunction and perhaps more recently pulmonary artery hypertension, less is known of their potential beneficial effects in other situations. Medeiros et al., in the current issue of the British Journal of Pharmacology, report that sildenafil dramatically reduces alcohol-induced gastric damage in rats. The authors provide convincing evidence that such protection not only occurs via the nitric oxide (NO)/cGMP pathway, but also involves regulation of ATP-sensitive potassium channels. Therefore, in addition to exerting anti-impotence efficacy, PDE V inhibitors may provide significant beneficial effects from mucosal injury induced by alcohol.
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PMID:Sildenafil reduces alcohol-induced gastric damage: just say 'NO'. 1807

In the presented case three herbal aphrodisiacs (Libidfit, Satibo and Viamax) were investigated for the presence of regular pharmaceuticals against erectile dysfunction. However, high-performance liquid chromatography with diode array detection and mass spectrometry (HPLC-DAD-MS) and nuclear magnetic resonance (NMR) analyses revealed the presence of ingredients, having a molecular structure strongly resembling those of sildenafil (Viagra) and vardenafil (Levitra). The health risk posed by these analogous substances is high because they were found to be potent phosphodiesterase 5 (PDE5) inhibitors used in pharmacologically relevant quantities having no known safety profile. Based on structural and functional analogy these analogs represent a new class of designer drugs and should be taken off the market for being unapproved drug substances. In the Libidfit court case this was done successfully, setting a precedent.
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PMID:Designer drugs in herbal aphrodisiacs. 1817 54

Sildenafil citrate (Revatio), an inhibitor of phosphodiesterase type 5 (PDE5), is approved for use in the US, Europe and other countries for the treatment of pulmonary arterial hypertension (PAH). Oral sildenafil 20 mg three times daily added to conventional background therapy was significantly more effective than placebo at increasing exercise capacity in patients with idiopathic PAH or PAH associated with connective tissue diseases or repaired congenital systemic-to-pulmonary shunts. Sildenafil was also associated with improvements in WHO functional class and haemodynamic parameters, and was generally well tolerated. Sildenafil provides benefits in terms of exercise capacity when added to epoprostenol; however, these findings come from a trial that did not use the approved dosage of sildenafil. In conclusion, sildenafil is an effective oral treatment option for patients with PAH.
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PMID:Sildenafil: a review of its use in pulmonary arterial hypertension. 1825 13

The purpose of this study was to identify the effect of sildenafil citrate on IL-1beta-induced nitric oxide (NO) synthesis and iNOS expression in human synovial sarcoma SW982 cells. IL-1? stimulated the cells to generate NO in both dose- and time-dependent manners. The IL-1beta-induced NO synthesis was inhibited by guanylate cyclase (GC) inhibitor, LY83583. When the cells were treated with 8-bromo-cGMP, a hydrolyzable analog of cGMP, NO synthesis was increased upto 5-fold without IL-1beta treatment suggesting that cGMP is an essential component for increasing the NO synthesis. Synoviocytes and chondrocytes contain strong cGMP phosphodiesterase (PDE) activity, which has biochemical features of PDE5. When SW982 cells were pretreated with sildenafil citrate (Viagra), a PDE5 specific inhibitor, sildenafil citrate significantly inhibited IL-1beta-induced NO synthesis and iNOS expressions. From this result, we noticed that PDE5 activity is required for IL-1?-induced NO synthesis and iNOS expressions in human synovial sarcoma cells, and sildenafil citrate may be able to suppress an inflammatory reaction of synovium through inhibition of NO synthesis and iNOS expression by cytokines.
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PMID:Effect of sildenafil citrate on interleukin-1beta-induced nitric oxide synthesis and iNOS expression in SW982 cells. 1858 66

Satisfaction with the sexual experience is considered important when evaluating the impact of treatments for erectile dysfunction, yet enhanced satisfaction has been infrequently assessed in the sexual trials. We evaluated the efficacy of sildenafil vs. tadalafil, in Saudi men with erectile dysfunction and determined the self-based rating of medicinal preference. Sildenafil citrate (Viagra) is a potent inhibitor of the electrolytic enzyme type V phosphodiesterase (PDE5), in the corpus cavernosum and therefore increases the penile response to sexual stimulation. Tadalafil (Cialis) is also a PDE5 inhibitor that increases the level of cyclic guanosine monophosphate (cGMP) in cavernous smooth muscle cells. Whereas cGMP is a second messenger for the vasodilator effects of nitric oxide causing smooth muscle relaxation, which in turn leads to penile erection; however the mechanism by which cGMP stimulates relaxation of the smooth muscles remains to be elucidated. Both sildenafil and tadalafil have a rapid onset with the effectiveness up to 4 hours and 36 hours respectively. In this study subjects treated with 100 mg oral dose of sildenafil / 20 mg tadalafil were found to be associated with higher mean scores for the questions of the International Index of Erectile Function (IIEF). Frequency of penetration and maintenance of erection after sexual penetration and/or during masturbation were found to be enhanced significantly (p<0.001) in both sildenafil/tadalafil treated men. Similarly mean domain of erectile function, orgasmic function, and intercourse satisfaction also showed a significantly positive improvement (p/0.001) in both the treated groups in comparison with their age matched untreated controls. Interestingly in all the cases, tadalafil group showed considerably greater positive responses than the sildenafil group but within the same significant levels. Strikingly the sexual-desire domain in sildenafil treated men with respect to their aged matched controls showed a non-significant difference, where as this difference was found to be highly significant in tadalafil treated group. Similarly mean scores for the overall satisfaction domains of the IIEF in comparison with the untreated subjects showed a significant positive response in the sildenafil treated group (p<0.001), where as tadalafil treated group showed a highly significant positive response (p<0.005). These findings suggest that both sildenafil and tadalafil may assist an individual in extending/enhancing the excitement phase or prolonging the sexual interaction. These studies further conclude that there is a major point of difference between the short-acting agent sildenafil and the longer acting tadalafil. This probably allows more choice about the onset of sexual responses with tadalafil than with sildenafil.
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PMID:Effectiveness of sildenafil citrate (Viagra) and tadalafil (Cialis) on sexual responses in Saudi men with erectile dysfunction in routine clinical practice. 1861 24

Pulmonary arterial hypertension (PAH) is serious and a progressive disease with relatively poor prognosis if not identified and treated early in children. In pediatric age group, the transition of the pulmonary circulation from fetal life to neonatal period plays a pivotal role to maintain the pulmonary vascular resistance to be low. In children with iPAH, acute drug response to vasodilator is more prominent than that in adult. But, prognosis is relatively poor. Recently, phosphodiesterase (PDE) 5 inhibitor (sildenafil, Viagra) and endothelin receptor antagonist (bosentan, Tracleer) in addition to prostacyclin used as a combination therapy can be used for this age population. The 5-year survival has been improved to > 80%. In this chapter, we focus on pathophysiological aspects and treatment strategy of idiopathic PAH, familial PAH, and PAH in the neonate (ex. PPHN).
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PMID:[Pulmonary arterial hypertension in pediatric age]. 1905 42

Sildenafil (Viagra), a cyclic guanosine monophosphate-degrading phosphodiesterase 5 inhibitor, induces headache and migraine. Such headache induction may be caused by an increased neuronal excitability, as no concurrent effect on cerebral arteries is found. In 13 healthy females (23+/-3 years, 70.3+/-6.6 kg), the effect of sildenafil on a visual (reversing checkerboard) and a hypercapnic (6% CO2 inhalation) response was evaluated using functional magnetic resonance imaging (fMRI, 3 T MR scanner). On separate occasions, visual-evoked potential (VEP) measurements (latency (P100) and maximal amplitude) were performed. The measurements were applied at baseline and at both 1 and 2 h after ingestion of 100 mg of sildenafil. Blood pressure, heart rate and side effects, including headache, were obtained. Headache was induced in all but one subject on both study days. Sildenafil did not affect VEP amplitude or latency (P100). The fMRI response to visual stimulation or hypercapnia was unchanged by sildenafil. In conclusion, sildenafil induces mild headache without potentiating a neuronal or local cerebrovascular visual response or a global cerebrovascular hypercapnic response. The implication is that sildenafil-induced headache does not include a general lowering of threshold for a neuronal or cerebrovascular response, and that sildenafil does not modulate the hypercapnic response in healthy subjects.
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PMID:Cerebral haemodynamic response or excitability is not affected by sildenafil. 1920 79

Female sexual arousal disorder (FSAD) is a common disorder encountered in clinical practice, with self-reported arousal difficulties reported in up to 26% of American women. Various oral therapies for FSAD have been studied, including sildenafil citrate, a phosphodiesterase inhibitor that is currently used to treat male erectile dysfunction. In vitro studies of sildenafil citrate have demonstrated smooth-muscle relaxation in clitoral tissue, and phosphodiesterase type-5 has been shown to be present in vaginal, clitoral and labial smooth muscle; these findings have led to theories that sildenafil citrate might be successful for treating FSAD. This Review discusses the data from clinical trials that have assessed sildenafil citrate for the treatment of FSAD; the trials show that sildenafil citrate is moderately effective. Sildenafil citrate may also be effective in women with FSAD secondary to multiple sclerosis, diabetes or antidepressant use; however, more trials in these patient populations are required to confirm these findings.
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PMID:Sildenafil citrate for female sexual arousal disorder: a future possibility? 1935 96

Data ascertained in a study of club drug use among 450 gay and bisexual men indicate that at least one class of PDE-5 (phosphodiesterase type 5 inhibitor, sildenafil [Viagra]) is used frequently in combination with club drugs such as methamphetamine, MDMA (3,4 methylenedioxymethamphetamine [ecstasy]), ketamine, cocaine, and GHB (gamma hydroxy butyrate). Patterns of sildenafil use in combination with each of the club drugs differ among key demographics including race and age. Multivariate models, controlling for demographic factors, suggest that contextual factors are key to understanding why men mix sildenafil with club drugs, although age may still be an important issue to consider. Of particular importance is the fact that use of club drugs in combination with sildenafil is strongly associated with circuit and sex parties, where a centerpiece of these environments focuses on sexual exchange. These models imply interplay between person-level and contextual factors in explaining drug use patterns and further indicate that interventions aimed at addressing illicit substance use must carefully consider the role of environmental factors in explaining behavior.
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PMID:Sildenafil (Viagra) and club drug use in gay and bisexual men: the role of drug combinations and context. 1948 90


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