Disease relevance of C07259

• Acute myocardial infarction after the use of sildenafil [1].
• BACKGROUND: The cardiovascular effects of sildenafil are important because of the frequent presence of underlying cardiac disease in men with erectile dysfunction and reports indicating serious cardiac events temporally associated with the use of this drug [2].
• The ratio of coronary flow reserve in coronary arteries with stenosis to that in the reference arteries (0.57+/-0.14) was not affected by sildenafil [2].
• Sildenafil also reverses pre-established hypertrophy induced by pressure load while restoring chamber function to normal. cGMP catabolism by PDE5A increases in pressure-loaded hearts, leading to activation of cGMP-dependent protein kinase with inhibition of PDE5A [3].
• The most common adverse events were headache (11% sildenafil, 2% placebo), dyspepsia (9% sildenafil, 0% placebo), and respiratory tract disorder (6% sildenafil, 2% placebo), predominantly sinus congestion or drainage [4].
• With close monitoring of blood pressure and heart rate, men with stable coronary artery disease who have taken sildenafil may tolerate intravenous NTG (<or=160 microg/min) with low starting dosage and gradual upward titration [5].

Psychiatry related information on C07259

• Sildenafil in the treatment of erectile dysfunction [6].
• Sildenafil use, sexual risk behavior, and risk for sexually transmitted diseases, including HIV infection [7].
• CONCLUSION: Sildenafil is a safe and effective treatment for ED in men with New York Heart Association classes II and III CHF and provides relief of depressive symptoms, explaining an improvement in the perception of quality of life [8].
• Transient global amnesia after sildenafil (Viagra) use [9].
• METHODS: A four-week double-blind crossover trial of sildenafil (50 mg up to 100 mg per usage) versus placebo was conducted on 21 outpatients diagnosed with chronic PTSD accompanied by ED [10].

High impact information on C07259

• Furthermore, a cGMP-enhancing agent, sildenafil, promoted vWF- or thrombin-induced platelet aggregation [11].
• Sildenafil in primary pulmonary hypertension [12].
• Hemodynamic effects of sildenafil in men with severe coronary artery disease [2].
• RESULTS: Oral sildenafil produced only small decreases (<10 percent) in systemic arterial and pulmonary arterial pressures, and it had no effect on pulmonary-capillary wedge pressure, right atrial pressure, heart rate, or cardiac output [2].
• Increased glomerular filtration rate in kidney-transplant recipients who take sildenafil [13].

Chemical compound and disease context of C07259

• The feasibility of these enzymes as drug targets is exemplified by the commercial and clinical successes of the erectile dysfunction drugs, sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) [14].
• Our aim was to compare acute effects of sildenafil, nitric oxide, and epoprostenol in individuals with pulmonary hypertension secondary to lung fibrosis [15].
• The introduction of sildenafil citrate, the first oral agent for the treatment of this disorder, has increased awareness about the risks of sexual activity in cardiac patients and raised concerns about the safety of sildenafil in patients being treated for coronary disease [16].
• When chronically administered from Days 14-28, sildenafil significantly increased plasma cyclic guanosine monophosphate and inhibited the development of pulmonary hypertension and right heart hypertrophy, with preservation of gas exchange and systemic arterial pressure [17].
• Efficacy of oral sildenafil in the treatment of erectile dysfunction in diabetic men with positive response to intracavernosal injection of alprostadil [18].

Biological context of C07259

• In the last four weeks of treatment in the dose-escalation study, 69 percent of all attempts at sexual intercourse were successful for the men receiving sildenafil, as compared with 22 percent for those receiving placebo (P<0.001) [19].
• After sildenafil use, resting systolic blood pressure was reduced from 135 (19) mm Hg to 128 (17) mm Hg, for a mean change of -7 mm Hg (95% confidence interval [CI], -9 to -4 mm Hg; P<.001) [20].
• INTERVENTION: Patients were randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks [21].
• Increased bioavailability of sildenafil in Mexican men [22].
• Safe sex for men with coronary artery disease: exercise, sildenafil, and risk of cardiac events [23].

Anatomical context of C07259

• Here, we show that blocking the intrinsic catabolism of cGMP with an oral phosphodiesterase-5A (PDE5A) inhibitor (sildenafil) suppresses chamber and myocyte hypertrophy, and improves in vivo heart function in mice exposed to chronic pressure overload induced by transverse aortic constriction [3].
• By removing these tumor escape mechanisms, sildenafil enhances intratumoral T cell infiltration and activation, reduces tumor outgrowth, and improves the antitumor efficacy of adoptive T cell therapy [24].
• In particular, sildenafil, down-regulates arginase 1 and nitric oxide synthase-2 expression, thereby reducing the suppressive machinery of CD11b(+)/Gr-1(+) myeloid-derived suppressor cells (MDSCs) recruited by growing tumors [24].
• Results: Lower esophageal sphincter tone, residual pressure, and wave amplitude after sildenafil showed a significant decrease compared with both the basal period and the placebo group, with a marked interpatient variability [25].
• Oral sildenafil is an effective and well-tolerated treatment for erectile dysfunction caused by spinal cord injury [26].

Associations of C07259 with other chemical compounds

• After inhalation of nitric oxide (10-20 ppm), we assigned patients to either maximum tolerated dose of intravenous epoprostenol (mean 8.0 ng/kg per min; n=8) or oral sildenafil (50 mg; n=8) [15].
• Vardenafil was 3 and 30 times more potent an inducer of apoptosis than sildenafil and MQZ, respectively [27].
• Following clinical improvement of one previously untreated CLL patient with sildenafil therapy, we evaluated the in vitro induction of apoptosis in CLL cells by 4 PDE5/6 inhibitors, including sildenafil, vardenafil, zaprinast, and methoxyquinazoline (MQZ) [27].
• High-fat-fed mice treated with sildenafil plus l-arginine or sildenafil alone for 12 weeks had reduced weight and fat mass due to increased energy expenditure [28].
• We report here the crystal structures of a fully active catalytic domain of unliganded PDE5A1 and its complexes with sildenafil or icarisid II [29].
• The suppressant effect of sildenafil on adrenergic transmission was attenuated in CC strips pretreated with N omega-nitro-L-arginine and overcome with a higher stimulus frequency or tetraethylammonium [30].
• Priming the patients with trazodone appears to be a reasonably good alternative in patients who have initial failure to oral sildenafil citrate and have been found to have no organic cause of ED [31].

Gene context of C07259

• Sildenafil-induced protection against necrosis and apoptosis was absent in the myocytes derived from iNOS knock-out mice and was attenuated in eNOS knock-out myocytes [32].
• The up-regulation of Bcl-2 expression by sildenafil was also absent in iNOS-deficient myocytes [32].
• To study the signaling pathways implicated in the sildenafil-stimulated angiogenic responses we determined the phosphorylation status of mitogen-activated protein kinase (MAPK) members [33].
• Incubation of cells with sildenafil increased both extracellular signal regulated kinase 1/2 (ERK1/2) and p38 phosphorylation in a time-dependent manner [33].
• The PDE5 inhibitor sildenafil produced vasorelaxant responses in isolated pulmonary arteries [34].
• In patients treated with PLC plus sildenafil, a decrease in ICAM-1, P-selectin, and EDV values was observed compared with patients treated with sildenafil alone (p<0.05, p<0.01, p<0.001, respectively) [35].
• Our study demonstrated for the first time a strong additional therapeutic potential of sildenafil by up-regulating VEGF and Ang-1 system, probably by stimulating a cascade of events leading to neovascularization and conferring myocardial protection in in vivo I/R rat model [36].

Analytical, diagnostic and therapeutic context of C07259

• For the men receiving 100 mg of sildenafil, the mean score for the question about achieving erections was 100 percent higher after treatment than at base line (4.0 vs. 2.0 of a possible score of 5) [19].
• Sildenafil and ocular perfusion [37].
• We evaluated the efficacy and safety of sildenafil, administered as needed in two sequential double-blind studies of men with erectile dysfunction of organic, psychogenic, and mixed causes [19].
• INTERVENTIONS: All patients underwent 2 symptom-limited supine bicycle echocardiograms separated by an interval of 1 to 3 days after receiving a single dose of sildenafil (50 or 100 mg) or placebo 1 hour before each exercise test [20].
• CONCLUSION: In men with stable CAD, sildenafil had no effect on symptoms, exercise duration, or presence or extent of exercise-induced ischemia, as assessed by exercise echocardiography [20].

References