Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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, the first internationally approved and widely used oral agent for the treatment of erectile dysfunction (ED), has revolutionized the treatment of ED throughout the past 5 years. This phosphodiesterase type-5 (PDE-5) inhibitor is selective for corpus cavernosum smooth muscle tissue and produces excellent erectile function. Its efficacy and safety over a wide variety of etiologies of ED and severities of ED demonstrates its usefulness in the clinical treatment of these patients. More than 20 million men have been treated worldwide with sildenafil with excellent results. ED caused by difficult-to-treat etiologies such as radical prostatectomy, severe diabetes, and spinal cord injury have demonstrated efficacy. Although sildenafil citrate, like all PDE-5 inhibitors, is contraindicated in patients taking nitrate medications for cardiac disease, it is effective and safe for those cardiovascular patients who are not taking nitrate medications. The incidence of adverse cardiovascular events in patients taking sildenafil does not differ from those of the general population. Investigations into the pharmacologic effect of sildenafil on coronary myocardial tissue further supports the safety of this medication. Sildenafil has been safe and effective in patients taking various medications including multiple antihypertensive drugs, selective serotonin reuptake inhibitors, cardiac, and diabetic medications.
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PMID:Sildenafil: a 4-year update in the treatment of 20 million erectile dysfunction patients. 1462 3

Erectile dysfunction (ED) is a commonly and frequently encountered disease among middle-aged and old males. The traditional Chinese medicine has a long history of medical treatment for ED has been focusing too much on clinical experience researches, without obtaining sufficient evidence for the curative effect of related traditional medicines. Recently, with important breakthroughs the researches on the molecular biochemical mechanisms of erection, sildenafil(Viagra), a phosphodiesterase type 5 (PDE5) inhibitor, has been developed, and exciting progress achieved in the treatment of ED with Chinese herbal medicine and the presentation of the pharmacological mechanism. This article presents an overview on recent advances in the studies of ED treatment with traditional Chinese medicine.
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PMID:[Advances in studies of Chinese herbs for improving relaxability of corporal smooth muscle]. 1468

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. Many drugs are now available for the treatment of ED, with oral pharmacotherapy representing the first-line option for most patients. Sildenafil citrate, an inhibitor of the enzyme phosphodiesterase type 5 (PDE5), is the most widely prescribed oral agent and has a very satisfactory efficacy-safety profile in all patient categories. Tadalafil (Cialis; Eli Lilly & Co., ICOS) and vardenafil (Levitra; Bayer Pharmaceuticals, GlaxoSmithKline) are new PDE5 inhibitors that have recently been approved worldwide. Both have been associated with significant positive efficacy-safety profiles. Apomorphine sublingual is a dopamine D1 and D2 receptor agonist, which has been approved for marketing in Europe. It is best selected for treating patients with mild-to-moderate ED, but it is seldom used in clinical practice due to its limited efficacy and side effects, particularly nausea. Patients who do not respond to oral pharmacotherapy or who are unable to use it are appropriate candidates for intracavernosal and intraurethral therapy. The efficacy of second-line treatment is high, but the attrition rate remains significant. For the purpose of this review, clinical and pharmacological analysis focuses on the recent advances in the field of oral therapy, including PDE5 inhibitors and sublingual apomorphine.
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PMID:Emerging oral drugs for erectile dysfunction. 1515 43

In 1998, we concluded that sildenafil (Viagra--fizer Ltd), a selective phosphodiesterase type 5 inhibitor, appeared to offer advantages over other medical approaches for erectile dysfunction in terms of ease of administration and cost. Oral drug treatment is now widely advocated as first-line therapy for erectile dysfunction, except where the cause is clearly psychological. In the past 4 years, three more oral preparations have been licensed in the UK for the treatment of men with erectile dysfunction. A sublingual preparation of the dopaminergic agonist apomorphine (Uprima--Abbott Laboratories Ltd) is the first centrally acting drug to be licensed. Tadalafil (Cialis--Eli-Lilly) and vardenafil (Levitra--Bayer PLC) are phosphodiesterase type 5 inhibitors. Here we review the place of these preparations for men with erectile dysfunction.
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PMID:New oral drugs for erectile dysfunction. 1527 71

Treatment strategies for pulmonary hypertension in children have dramatically evolved. Traditional therapy with calcium channel blockers and pulmonary transplantation is only indicated in selected patients and does not reduce mortality very significantly. New pulmonary vasodilators are emerging from recent trials in the adult population. Their indications are based on the patient's NYHA classification. The epoprostenol (prostacyclin, Flolan) has shown reduction in mortality and improvement in functional symptoms in pediatric patients. The frequent side effects and continuous intravenous infusion limit the indication of prostacyclin in NYHA class IV children. The endothelin receptor blocker bosentan (Tracleer) is an orally given agent. It improves functional symptoms in adults and hemodynamic measures in children. It can be started in children with moderate functional symptoms (NYHA class II and III). The type V phosphodiesterase inhibitor sildenafil (Viagra) is being evaluated and may represent a promising therapy in the future. Invasive strategies like catheter-based atrial septostomy may be useful in particular cases. Randomized-controlled studies are urgently needed to evaluate the safety and efficacy of these new therapies.
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PMID:[Treatment of pulmonary arterial hypertension in children]. 1528 88

Since the etiology of erectile dysfunction is frequently related to endothelial dysfunction, a problem in common with much vascular disease, erectile dysfunction disproportionately affects patients with cardiovascular disease. With the development of phosphodiesterase 5 inhibitors, the first of which was sildenafil (Viagra), an effective oral medication became available. The question of safety of these drugs, especially in patients with latent or overt coronary artery disease, is of concern. Sildenafil relaxes smooth muscle and therefore lowers systolic and diastolic blood pressure slightly. With organic nitrates, the drop in blood pressure is potentiated, at times dangerously, thereby making it contraindicated to take nitrates within 24 hours of using sildenafil. In double-blind, placebo-controlled trials, there was no difference between sildenafil subjects and control patients in the incidence of myocardial infarction, cardiovascular, and total deaths. Coronary disease patients with stable angina, controlled on medications, were included in the trials. Therefore, sildenafil, as a drug, is safe in such patients. With a patient with coronary artery disease suddenly engaging in the physical exercise associated with sexual intercourse, there is the danger of increased risk of precipitating myocardial infarction or death. The cardiovascular metabolic cost of sexual activity is reviewed and appears to be approximately at the level of 3-5 metabolic equivalents of exercise. Sexual activity occurs within 2 hours of the onset of an acute myocardial infarction in <1.0% of patients. Although sexual intercourse is estimated to increase the risk of myocardial infarction by a factor of 2x, there is still only a very small increase in risk, a risk acceptable to patients who feel their quality of life will be markedly improved by their ability to engage in sexual activity.
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PMID:Should the patient with coronary artery disease use sildenafil? 1531 86

A five-month-old girl of Down syndrome underwent a corrective surgery for complete atrioventricular septal defect. Her postoperative course was complicated with pulmonary hypertensive (PH) crises despite nitroglycerin (NTG) infusion and inhaled nitric oxide (NO). Sildenafil citrate, a phosphodiesterase 5 inhibitor, was administered through a nasogastric tube at a starting dose of 0.3 mg/kg by stepwise increment to the maximum dose of 2 mg/kg 4 hourly. Sildenafil citrate dramatically lowered pulmonary arterial pressure and the patient was weaned from NTG and NO without PH crisis. There was no side effect after sildenafil citrate administration. Oral sildenafil citrate is a safe and potent adjunct to the existing therapies for postoperative PH in infants after open heart surgery.
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PMID:[Oral sildenafil citrate as an effective alternate in the treatment of postoperative pulmonary hypertensive crisis after congenital heart surgery]. 1536 67

The physiological role of phosphodiesterase (PDE)11 is unknown and its biochemical characteristics are poorly understood. We have expressed human His-tagged PDE11A4 and purified the enzyme to apparent homogeneity. PDE11A4 displays K(m) values of 0.97 microM for cGMP and 2.4 microM for cAMP, and maximal velocities were 4- to 10-fold higher for cAMP than for cGMP. Given the homology between PDE11 and PDE5, we have compared the biochemical potencies of tadalafil (Cialis, Lilly-ICOS), vardenafil (Levitra, Bayer-GSK), and sildenafil (Viagra, Pfizer Inc.) for PDE11A4 and PDE5A1. PDE5A1/PDE11A4 selectivities are 40-, 9300-, and 1000-fold for tadalafil, vardenafil, and sildenafil, respectively. This suggests that none of these three compounds is likely to crossreact with PDE11A4 in patients.
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PMID:High biochemical selectivity of tadalafil, sildenafil and vardenafil for human phosphodiesterase 5A1 (PDE5) over PDE11A4 suggests the absence of PDE11A4 cross-reaction in patients. 1599 18

Purine bases and their bioisosteric analogs are widely used as building blocks in combinatorial chemistry. Recently a great number of fused pyrimidine derivatives became known as potential drug molecules against various types of proliferative diseases, caused by over-expression of protein kinases. One of the most important compound families are quinazolines : e.g. the best inhibitor of EGFR tyrosine kinase is PD153035 (6,7-dimethoxy-4-(3'-bromophenyl)amino-quinazoline) and IRESSA (gefitinib, ZD1839), developed from this compound family, is presently the only one approved and granted drug by the FDA for the treatment of advanced non-small-cell lung cancer (NSCLC). KF31327 (3-ethyl-8-[2-(4-hydroxymethylpiperidino)benzylamino]-2,3-dihydro-1H-imidazo[4,5-g]-quinazoline-2-thione dihydrochloride) from this group, showed significantly higher inhibitory activity on cyclic GMP-specific phosphodiesterase compared with those of sildenafil (Viagra). The synthetic procedures of the example compounds are based on imidoyl chloride intermediates that were prepared from the appropriate 3H-quinazoline-4-ones. Although the key intermediates, quinazoline-4-ones, have been known since more than hundred years, their synthetic procedures have been improved much only in the past ten years. In this paper we reviewed the efficient synthetic methods of quinazolin-4-ones, and presented a novel, reliable method for their synthesis. There was no considerable effect of microwave-, or traditional thermal activation on the yield and compound purity.
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PMID:Improved, high yield synthesis of 3H-quinazolin-4-ones, the key intermediates of recently developed drugs. 1554 62

Sildenafil (Viagra), a selective and specific inhibitor of cyclic guanosine monophosphate (cGMP) phosphodiesterases (PDEs), is currently marketed for the treatment of erectile dysfunction. Sildenafil is a potent and highly selective PDE-V inhibitor and enhances smooth muscle relaxation in human. Systemic arterial and venous smooth muscle cells contain PDE-V and nitric oxide (NO) which is a major mediator of relaxation of the smooth muscle cell. The aim of the present study is to investigate, in a rat model, the potential effect of sildenafil on survival of random pattern skin flaps. For this purpose, 32 Sprague-Dawley rats were used and a McFarlane-type caudally based skin flap was designed on the dorsum of the rat (2.5 x 8 cm). Rats were divided into four groups: One control (Group D), and three treatment groups (Groups A, B, C). Sildenafil was administered orally to the experiment groups; Group A: 3 mg/kg/single dose a day, Group B: 10 mg/kg/single dose a day and Group C: 10 mg/kg/twice dose a day. The areas of flap necrosis were measured in each group. The extent of viable flap areas were expressed as a percentage of total flap area, and differences were studied by Completely Randomised Experimental design. The areas of necrosis of skin flaps decreased depending on sildenafil dose, but viability of the flaps treated with 3 mg/kg/day was not different than the control group. The flaps receiving 2 x 10 mg/kg/day sildenafil gave the highest (P < 0.01) survival rate. As a conclusion, sildenafil may have a dose dependent effect to increase flap survival in random skin flaps.
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PMID:The influence of sildenafil on random skin flap survival in rats: an experimental study. 1554 75


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