Disease relevance of Levitra

• Sildenafil and vardenafil, types 5 and 6 phosphodiesterase inhibitors, induce caspase-dependent apoptosis of B-chronic lymphocytic leukemia cells [1].
• Phosphodiesterase-5 (PDE5) is the target for sildenafil, vardenafil, and tadalafil, which are drugs for treatment of erectile dysfunction and pulmonary hypertension [2].
• The most commonly reported adverse events (typical of those seen with PDE5 inhibitors) in vardenafil 5-20 mg recipients included headache, flushing, rhinitis, dyspepsia and sinusitis [3].
• Vardenafil improved erectile function in men with ED associated with diabetes mellitus or ED following unilateral or bilateral nerve-sparing radical retropubic prostatectomy in two randomised, double-blind, multicentre, fixed-dose, 3-month studies [3].
• Phosphodiesterase-5 (PDE-5) inhibitors including sildenafil and vardenafil induce powerful preconditioning-like cardioprotective effect against ischemia/reperfusion injury through opening of mitochondrial K(ATP) channels in the heart [4].

Psychiatry related information on Levitra

• 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) [5].
• After 12 weeks, vardenafil-treated patients with severe ED showed a significant improvement in their self-esteem compared with patients receiving placebo (change from baseline -1.51 vs. 3.54, respectively, P = 0.036) [6].
• All 3 doses of vardenafil were superior to placebo across all primary efficacy variables and all study time points in a broad range of patients with ED, regardless of etiology or severity [7].

High impact information on Levitra

• It is concluded that Gln(817) is a positive determinant for PDE5 affinity for cGMP and several inhibitors; Gln(775), which perhaps restricts rotation of Gln(817) side chain, is critical for cGMP affinity but has no measurable effect on affinity for cAMP, sildenafil, or vardenafil [8].
• Digital blood flow was measured by laser-Doppler flowmetry at room temperature and during the cold-exposure test before medical treatment, 1 hour after the initial intake, and after 2 weeks of continuous treatment (10 mg twice a day) with the novel phosphodiesterase type 5 inhibitor vardenafil [9].
• Sildenafil and tadalafil, but not vardenafil, caused a significant reduction in the pulmonary to systemic vascular resistance ratio [10].
• At peak exercise, vardenafil 10 mg did not alter blood pressure, heart rate, or rate-pressure product relative to placebo [11].
• CONCLUSIONS: Vardenafil 10 mg did not impair the ability of patients with stable CAD to exercise at levels equivalent or greater than that attained during sexual intercourse (average of 2.5 to 3.3 METS) [11].

Chemical compound and disease context of Levitra

• Sildenafil and vardenafil but not nitroglycerin limit myocardial infarction through opening of mitochondrial K(ATP) channels when administered at reperfusion following ischemia in rabbits [4].
• Although phosphodiesterase type 5 inhibitors are safe when administered with most medications, sildenafil given with doxazosin and vardenafil given with terazosin evoke orthostatic hypotension in some patients [12].
• BACKGROUND: The efficacy and tolerability of vardenafil hydrochloride in men with erectile dysfunction (ED) and a history of nonresponse to sildenafil citrate have previously been reported [13].
• The results show that the erectile dysfunction induced by paroxetine in rats can be effectively treated with vardenafil, suggesting that the use of this compound could be a reasonable therapeutic approach to treating erectile dysfunction associated with SSRI administration [14].
• This flow amplification during acidosis was not shared by the K(ATP) channel opener cromakalim, indicating a specific effect of vardenafil on flow control during myocardial acidosis [15].

Biological context of Levitra

• RESULTS: All three PDE5 inhibitors caused significant pulmonary vasorelaxation, with maximum effects being obtained after 40 to 45 min (vardenafil), 60 min (sildenafil), and 75 to 90 min (tadalafil) [10].
• CONCLUSIONS: In PAH patients, the three PDE5 inhibitors differ markedly in their kinetics of pulmonary vasorelaxation (most rapid effect by vardenafil), their selectivity for the pulmonary circulation (sildenafil and tadalafil, but not vardenafil), and their impact on arterial oxygenation (improvement with sildenafil only) [10].
• Binding of tritiated sildenafil, tadalafil, or vardenafil to the phosphodiesterase-5 catalytic site displays potency, specificity, heterogeneity, and cGMP stimulation [16].
• A 46-Amino Acid Segment in Phosphodiesterase-5 GAF-B Domain Provides for High Vardenafil Potency over Sildenafil and Tadalafil and Is Involved in Phosphodiesterase-5 Dimerization [17].
• Sildenafil and vardenafil are shorter-acting agents, while tadalafil has a longer half-life allowing the user more flexibility in sexual activity [18].

Anatomical context of Levitra

• The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease [11].
• Both sildenafil and vardenafil protect the ischemic myocardium against reperfusion injury through a mechanism dependent on mitochondrial K(ATP) channel opening [4].
• OBJECTIVES: To evaluate the levels of circulating progenitor cells (PCs) and the effect of a single dose of vardenafil 20mg on the number of these cells in men with erectile dysfunction (ED) and various degree of vascular injury at the carotid artery level [19].
• Relationship Between Vascular Damage Degrees and Endothelial Progenitor Cells in Patients with Erectile Dysfunction: Effect of Vardenafil Administration and PDE5 Expression in the Bone Marrow [19].
• Vardenafil also significantly potentiated both ACh-induced and transmural electrical stimulation-induced relaxation of trabecular smooth muscle [20].

Associations of Levitra with other chemical compounds

• The goal of these studies was to demonstrate the protective effect of sildenafil and vardenafil on reperfusion injury and to compare it with the antianginal vasodilator nitroglycerin (NTG) [4].
• The Food and Drug Administration (FDA) approved PDE-5 inhibitors include sildenafil citrate, vardenafil hydrochloride and tadalafil [21].
• Single-dose vardenafil 20 mg was administered in a randomized four-way crossover design after an overnight fast (at 8 a.m.), after consumption of a high-fat breakfast (at 8 a.m.), on an empty stomach (at 6 p.m.), and after a typical moderate-fat evening meal (at 6 p.m.). Serial blood samples were analyzed for vardenafil and metabolite (M1) levels [22].
• Vardenafil, vardenafil metabolite M-1 and ethanol pharmacokinetics were assessed [23].
• The relaxation of L-noradrenaline-contracted female human urethra was 100% in response to 10 microm sildenafil, and 85 (15)% and 47 (13)% for 30 microm of vardenafil and tadalafil, respectively (three samples) [24].

Gene context of Levitra

• The phosphodiesterase inhibitory selectivity and the in vitro and in vivo potency of the new PDE5 inhibitor vardenafil [20].
• In contrast, the IC50 of vardenafil for PDE1 was 180 nM; for PDE6, 11 nM; for PDE2, PDE3 and PDE4, more than 1000 nM [20].
• 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) [25].
• The hypothesis was tested that vardenafil, a PDE5 inhibitor, specifically enhances coronary vasodilation during acidosis [15].
• METHODS: In this double-blind, crossover, single-dose multicenter study, 41 men with reproducible stable exertional angina due to ischemic CAD received vardenafil 10 mg or placebo, followed by ETT (5 to 10 metabolic equivalents [METS], Bruce protocol) 1 h postdose [11].

Analytical, diagnostic and therapeutic context of Levitra

• METHOD: In this 12-week, multicenter, randomized, flexible-dose, parallel-group, double-blind study, 280 men with erectile dysfunction for at least 6 months and untreated mild major depression received placebo or vardenafil, 10 mg/day, for 4 weeks, with the option to titrate to 5 mg/day or 20 mg/day after each of two consecutive 4-week intervals [26].
• RESULTS: Laser-Doppler flowmetry revealed that vardenafil improved digital blood flow in 28 (70%) patients, whereas 12 (30%) did not respond [9].
• CONCLUSIONS: The effect of vardenafil on penile erection after oral administration was clearly demonstrated in the conscious rabbit model [27].
• High performance liquid chromatography and mass spectrometry were used to detect evidence of contamination with sildenafil, tadalafil or vardenafil [28].
• METHODS: Twenty-one patients with erectile dysfunction completed three oral single-dose regimens (placebo, 20 and 40 mg vardenafil) in a randomized, placebo-controlled, 3-way cross-over study [29].

References