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)

Vardenafil is a new oral phosphodiesterase inhibitor used for erectile dysfunction. We report a case admitted with a first-detected, symptomatic paroxysmal atrial fibrillation in a healthy patient after self-medication with vardenafil.
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PMID:Atrial fibrillation after vardenafil therapy. 1624 51

More treatment options are available now for the treatment of erectile dysfunction (ED) than ever. Treatments include oral phosphodiesterase 5 (PDE5) inhibitors, intracavernosal injections, vacuum constriction devices, and penile implants. Clinicians, researchers, and patients are interested in making direct comparisons between the response of newer treatments and that of established and more developed therapies. Of the currently available treatment options for ED, the most commonly prescribed therapies are oral PDE5 inhibitors, which include sildenafil citrate (Viagra, Pfizer Inc), tadalafil (Cialis, Lilly ICOS), and vardenafil (Levitra, Bayer). However, most patient preference studies of these drugs conducted to date have serious design flaws that hinder interpretation of the data, and thus limit the utility of the results. To make an informed decision on the most appropriate treatment option available, physicians and their patients require a thorough understanding of the methodology of these studies. Clinical comparison or preference trials must establish internal and external validity if the data are to be used in a generalized patient population. We review preference studies that compared sildenafil, tadalafil, and vardenafil, and highlight study designs that can introduce bias. We propose that, like safety and efficacy trials, randomized controlled trials (RCTs) should be the gold standard for evaluating patient preference treatments for ED. We do not wish to discourage individual investigators from performing preference studies, but rather to highlight the features of current preference trials to help patients and clinicians alike become aware of potential biases from independent or industry-sponsored patient preference trials so that they can interpret the results accordingly. Key components of patient preference RCTs are reviewed: period and carryover effects, preference assessments, eligibility criteria, and data analysis. We discuss why these components of patient-preference RCTs are important for evaluating the validity and relevance of patient preference studies. The preference studies discussed in this brief review are summarized in , and the methodological problems with each study are indicated. We provide a recommendation for the design of such trials that can minimize bias and provide better data for physicians and their patients.
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PMID:Evaluating preference trials of oral phosphodiesterase 5 inhibitors for erectile dysfunction. 1626 7

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men. At present, first-line oral pharmacotherapy for most patients with ED is a phosphodiesterase type 5 (PDE-5) inhibitor, of which three are currently available worldwide. Sildenafil (Viagra, Pfizer) has a very satisfactory efficacy-safety profile in all patient categories. The first PDE-5 inhibitor to reach the market, it is now the most widely prescribed oral agent for ED. Tadalafil (Cialis, Lilly ICOS) and vardenafil (Levitra, Bayer/GlaxoSmithKline) were introduced to the European Union and the US in 2003 and 2004, respectively. These three PDE-5 inhibitors share many characteristics, but each has unique features. This review describes the chemical, pharmacologic and clinical features of sildenafil, vardenafil and tadalafil as oral first-line treatments for ED. First, we describe the physiology of penile erection and PDE-5 inhibitor pharmacology, including chemistry, PDE selectivity, pharmacokinetics, and possible drug interactions. We then summarize data on the efficacy and safety profiles of the three PDE-5 inhibitors for the treatment of ED in the general population, in patients with diabetes mellitus and in men that have undergone bilateral nerve-sparing retropubic radical prostatectomy.
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PMID:Drug Insight: oral phosphodiesterase type 5 inhibitors for erectile dysfunction. 1647 35

cGMP and opening of mitochondrial K(ATP) channel play an important role in preconditioning of the heart following ischemia/reperfusion (I/R) injury. We investigated the cardioprotective effect of vardenafil (VAR) (Levitra), a highly selective and biochemically potent inhibitor of phosphodiesterase-5 (PDE-5) that enhances erectile function in men through up-regulation of cGMP. Rabbits were treated with VAR (0.014 mg/kg, iv) or volume-matched saline, 30 min prior to 30 min of sustained regional ischemia followed by 3 h of reperfusion. 5-hydroxydecanoate (5-HD, 5 mg/kg, iv) or HMR 1098 (HMR, 3 mg/kg, iv), the respective blockers of mitochondrial or sarcolemmal K(ATP) channels were administered 10 min before I/R. Infarct size was measured by computer morphometry of tetrazolium stained sections. Vardenafil treatment caused decrease in mean arterial blood pressure from 93.5+/-2.6 to 82.2+/-1.5 mmHg and increase in heart rate from baseline value of 151+/-20 to 196+/-4.6 bpm (mean+/-standard error of mean (S.E.M.), P<0.05) within 5 min. The infarct size (% of risk area) was reduced from 33.8+/-1.3 in control rabbits to 14.3+/-2.2 (58% reduction, P<0.05). 5-HD abolished VAR-induced protection as demonstrated by increase in infarct size to 34.5+/-2.3 (P<0.05, N=6 per group). In contrast, HMR failed to block the protective effect of VAR (infarct size, 14.3+/-2.2 versus 16.3+/-1.0 in VAR + HMR, P>0.05). Neither inhibitors of the K(ATP) channel influenced the infarct size in the control rabbits, as shown by infarct size of 34.9+/-1.1 and 33.3+/-1.4 in animals treated with 5-HD and HMR, respectively. For the first time, we demonstrate that VAR induces protective effect against I/R injury via opening of mitochondrial K(ATP) channel. These results further support our hypothesis that the novel class of PDE-5 inhibitors induce protective effect in the ischemic heart, in addition to their well known clinical effects in the treatment of erectile dysfunction in men.
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PMID:Vardenafil: a novel type 5 phosphodiesterase inhibitor reduces myocardial infarct size following ischemia/reperfusion injury via opening of mitochondrial K(ATP) channels in rabbits. 1648 Jul 39

The introduction of oral agents for the treatment of erectile dysfunction (ED) has revolutionized the treatment of men with erection problems of all severities and etiologies. Sildenafil, available on the world market since 1998 was joined in 2003 by tadalafil and vardenafil as effective save and reliable oral agents. While these agents share the method of action in common and are all contraindicated with nitrate medications, these are differences among the three agents. Sildenafil has the longest patient experience and the most robust data confirming its activity, safety and tolerability. It has recently been released for use in pulmonary hypertension as well as ED. Vardenafil, the most biochemically potent of the molecules has also been demonstrated to be effective in men with severe ED and in some patients failing sildenafil. Tadalafil is unique in its longer half life and is also tolerable, safe and effective in all severities and etiologies of ED. Tadalafil is also unique in its inhibition of PDE 11, a characteristic of unknown but probably negligible importance. Newer data have also suggested that these agents may be helpful in the treatment of lower urinary tract symptoms. Since the introduction of sildenafil in 1998, erectile dysfunction has been effectively treated with oral medications. The recent addition of vardenafil and tadalafil to the market has increased the number of phosphodiesterase type 5 inhibitors (PDE5) to three agents used throughout the world. Each of these agents has similar mechanism of action, but has distinct differences. All three drugs in this class have similar pharmacokinetic and pharmacodynamic profiles and each is effective for patients with ED of all ages, severities and etiologies. While there are clear pharmacokinetic and pharmacodynamic differences amongst these agents, clinical differences are somewhat more difficult to identify. Indeed the data of preference trials, head to head clinical trials, and selection trials are few. The differences in pharmacokinetics while having distinct advantages in marketing each drug may be difficult for clinicians and patients to identify. With the lack of data and well done clinical trials, it is difficult for the clinician to differentiate amongst the three agents and to select a PDE5 inhibitor for a specific ED patient or a specific agent to switch to if an initial PDE5 agent is unsuccessful or poorly tolerated. This discussion summarizes some of the current data on PDE5 inhibitors and their efficacy, safety, and use in other conditions.
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PMID:PDE5 inhibitors: are there differences? 1652 79

This paper reviewed the efficacy and safety of vardenafil, a highly selective phosphodiesterase type 5 (PDE 5) inhibitor, in men with erectile dysfunction who were difficult to treat. Several large-scale studies indicated vardenafil was effective and safe in the treatment of these difficult-to-treat ED patients, including ED with depression or diabetes, ED after radical retropubic prostatectomy, ED caused by spinal cord injury, and sildenafil nonresponders. Vardenafil provides a rational treatment alternative.
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PMID:[Efficacy and safety of vardenafil in difficult-to-treat erectile dysfunction men]. 1668 77

The therapeutic and commercial success of phosphodiesterase 5 inhibitors such as Viagra, Levitra and Cialis has sparked renewed interest in the phosphodiesterases as drug discovery targets. Virtually all the phosphodiesterases are expressed in the CNS, making this gene family a particularly attractive source of new targets for the treatment of psychiatric and neurodegenerative disorders. Significantly, all neurons express multiple phosphodiesterases, which differ in cyclic nucleotide specificity, affinity, regulatory control and subcellular compartmentalization. Therefore, phosphodiesterase inhibition represents a mechanism through which it could be possible to precisely modulate neuronal activity. In this article, we review the current state of the art in the burgeoning field of phosphodiesterase pharmacology in the CNS.
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PMID:Phosphodiesterases in the CNS: targets for drug development. 1688 4

Reliable efficacy is very important to continuing treatment for patients with erectile dysfunction. Vardenafil is a potent, highly selective phosphodiesterase 5 (PDE5) inhibitor. The efficacy and safety of vardenafil has been confirmed in many clinical studies. This paper analyzed the efficacy reliability of vardenafil in clinical trials and real-life practice, concluded that it provided reliable efficacy for key parameters of erection and improved treatment compliance.
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PMID:[Reliable efficacy of vardenafil for treatment of erectile dysfunction]. 1689 50

Erectile dysfunction (ED) is a widespread, age-related medical condition that affects > 50% of men aged 40 - 70 years. Pharmacotherapy with orally available phosphodiesterase 5 (PDE5) inhibitors offers a convenient and simple approach to treatment. Results of numerous clinical trials have demonstrated significant efficacy in restoring the ability to achieve and sustain an erection, and adverse side effects are generally mild-to-moderate in severity. Vardenafil is a highly selective, potent PDE5 inhibitor developed for the treatment of ED. The potency and selectivity of vardenafil for PDE5 and other PDE isoforms have been evaluated in vitro and in vivo and compared with other compounds in the class. This review will discuss the findings of biochemical, in vitro and in vivo experiments that indicate the superior potency and high selectivity of vardenafil.
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PMID:Potency and selectivity of vardenafil: a phosphodiesterase Type 5 inhibitor. 1692 44

Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that regulate the cellular levels of the second messengers, cAMP and cGMP, by controlling their rates of degradation. There are 11 different PDE families, with each family typically having several different isoforms and splice variants. These unique PDEs differ in their three-dimensional structure, kinetic properties, modes of regulation, intracellular localization, cellular expression, and inhibitor sensitivities. Current data suggest that individual isozymes modulate distinct regulatory pathways in the cell. These properties therefore offer the opportunity for selectively targeting specific PDEs for treatment of specific disease states. 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). PDE inhibitors are also currently available or in development for treatment of a variety of other pathological conditions. In this review the basic biochemical properties, cellular regulation, expression patterns, and physiological functions of the different PDE isoforms will be discussed. How these properties relate to the current and future development of PDE inhibitors as pharmacological agents is especially considered. PDEs hold great promise as drug targets and recent research advances make this an exciting time for the field of PDE research.
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PMID:Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. 1696 49


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