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 potently inhibits human phosphodiesterase 5 (PDE5) with an IC50 of 0.7 nM. Enhancement of nitric oxide (NO)-induced erections in rabbits by 0.1 mg/kg vardenafil is limited by its pharmacokinetic properties (Tmax=1 h; T1/2=1.2 h), although erectile effects have been observed after 7 h. In humans, vardenafil is rapidly absorbed (Tmax approximately 40 min) and more slowly metabolized (T1/2 approximately 4 h), with an absolute bioavailability of 14.5% (vs 40% for sildenafil). Although the consumption of high-fat meals does not affect the drug's relative bioavailability, it retards intestinal absorption. Coadministration of CYP3A4 inhibitors such as ritonavir can affect hepatic metabolism. M1, an active metabolite of vardenafil, is a four-fold-less potent inhibitor of PDE5 than its parent compound, contributing approximately 7% to vardenafil's overall efficacy. The side effects of all selective PDE5 inhibitors commonly include vasodilation, small reductions in blood pressure, headache, and nasal congestion.
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PMID:Vardenafil preclinical trial data: potency, pharmacodynamics, pharmacokinetics, and adverse events. 1522 34

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

Vardenafil is a new phosphodiesterase type-5 inhibitor for the treatment of men with erectile dysfunction (ED). It was licensed in Europe in spring 2003 and in the USA in late 2003. It is a potent and selective inhibitor of the enzyme phosphodiesterase type 5, and in the presence of an erectile stimulus potentiates the intracellular actions of cyclic guanylate monophosphate. Several large, placebo-controlled trials have demonstrated efficacy both in the broad population of men with ED and in men with more difficult to treat ED. It is well tolerated with a side effect profile typical of this class of drugs. It has a rapid onset of action and has demonstrable efficacy for men using the medication for up to 2 years.
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PMID:Vardenafil: a new oral treatment for erectile dysfunction. 1537 54

Vardenafil is an oral, potent, highly selective phosphodiesterase 5 (PDE5) inhibitor. It improves erectile function significantly regardless of the etiology and severity of erectile dysfunction (ED) or the age of the patients. Its onset time leading to successful intercourse is as short as 10 minutes after administered orally, and in most patients it works persistently. Adverse reactions are generally transient and mild to moderate in nature. So vardenafil is both effective and safe for men with ED.
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PMID:[Efficacy and safety of vardenafil for men with erectile dysfunction]. 1549 16

Vardenafil is a potent and highly selective phosphodiesterase type 5 (PDE5) inhibitor with a potency about 10-fold higher than sildenafil. Vardenafil can significantly improve erectile function and works rapidly. Vardenafil is a PDE5 inhibitor with the fastest onset of action among its kind so far found and works as early as 10 minutes after oral administration, providing patients with penile erection sufficient to complete an intercourse. The absolute oral bioavailability is about 15%. Vardenafil is rapidly absorbed with a median tmax of 0.7 h and a terminal half-life (t1/2) of more than 4 h. The observed pharmacodynamic properties, pharmacokinetic characteristics and good safety and tolerability profile showed that vardenafil treatment provides an effective and generally well tolerated treatment for ED.
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PMID:[Pharmacodynamics and pharmacokinetics of vardenafil in patients with erectile dysfunction]. 1549 17

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

The prevalence of erectile dysfunction (ED) is higher in diabete patients than in non-diabete men. Moreover, the treatment of ED is more challenging in men with diabetes. Vardenafil, a novel and highly selective phosphodiesterase 5 inhibitor, is the first line therapy for the broad ED population. Recent large-scale clinical trials indicated that vardenafil improved erectile function in ED men with diabetes regardless of the baseline ED severity and plasma HbA1c levels, and it was generally well tolerated.
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PMID:[Vardenafil for the treatment of erectile dysfunction in men with diabetes]. 1556 98

Erectile dysfunction (ED) usually exists in combination with depression in men. The comorbidity of the two diseases may bring more troubles to patients, so it is important to find an effective treatment. Recently, DRIVER (Depression Related Improvement with Vardenafil for Erectile Response) trials showed that, phosphodiesterase 5 (PDE 5) inhibitor vardenafil could improve not only erectile function but also depressive symptoms and quality of life in men with ED and depression. Vardenafil was generally safe and well tolerated.
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PMID:[Efficacy and safety of vardenafil in men with erectile dysfunction and depression]. 1559 95

Erectile dysfunction (ED) affects up to 50% of men, between 40 and 70 years of age. In the first major trial of sildenafil in ED, at 24 weeks, improved erections were reported by 77 and 84% of men taking sildenafil 50 and 100mg, respectively. Subsequently, sildenafil has been reported to be effective in men with ED associated with diabetes and prostate cancer, and in psychogenic ED. Sildenafil is safe in men with coronary artery disease, provided it is not used with the nitrates (a contraindication). The most commonly reported adverse effects with sildenafil are headache, flushing and dyspepsia. Vardenafil is more potent and more selective than sildenafil at inhibiting phosphodiesterase-5. Vardenafil is similarly effective to sildenafil in the treatment of ED. The only advantage that vardenafil has over sildenafil is that it does not inhibit phosphodiesterase-6 to alter colour perception, a rare side effect which sometimes occurs with sildenafil. Tadalafil has a longer duration of action than sildenafil and vardenafil. Tadalafil is similarly effective as sildenafil in the treatment of ED. In comparison studies, tadalafil is preferred to sildenafil (50/100mg) by men with ED, possibly because of its longer duration of action. Of the phosphodiesterase inhibitors, tadalafil may displace sildenafil as the drug of choice among men with ED.
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PMID:Comparison of clinical trials with sildenafil, vardenafil and tadalafil in erectile dysfunction. 1570 77

[3H]Vardenafil (Levitra) or [3H]tadalafil (Cialis) binding was used to quantify PDE5 in rat lung and heart tissue. Each radioligand bound to purified recombinant phosphodiesterase-5 (PDE5) or to PDE5 in crude extracts with strong affinity, high specificity, slow dissociation, and good stoichiometry. PDE5, the only 3H inhibitor-binding protein detected in extracts, was 15 times higher in lung than in heart extracts, and the level measured by PDE5 catalytic activity agreed with that determined by 3H inhibitor binding. High level of PDE5 in lung approximated that in penile corpus cavernosum, the tissue targeted by PDE5 inhibitors. PDE5 was the predominant cGMP-PDE in lung, and on a molar basis was five times higher than cGMP-dependent protein kinase (PKG), which phosphorylates PDE5 in vivo. The PDE5 level was one-half that of PKG in heart. Thus, abundance of PDE5 in lung vascular smooth muscle provides a strong molecular basis for PDE5 inhibitor treatment of pulmonary hypertension.
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PMID:High lung PDE5: a strong basis for treating pulmonary hypertension with PDE5 inhibitors. 1602 93


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