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Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. Many drugs are now available for treating ED; oral pharmacotherapy represents the first-line option for most patients with ED. Sildenafil, an inhibitor of the enzyme phosphodiesterase type 5, is currently the most widely prescribed oral agent and has a very satisfactory efficacy-safety profile in all patient categories. Apomorphine SL is a dopamine D1- and D2-receptor agonist which has recently been approved for marketing in Europe. It is best selected for treating patients with mild to moderate ED. Vardenafil and tadalafil are new phosphodiesterase type 5 inhibitors which are expected to be approved this year. Both of them have significant positive efficacy-safety profiles. Patients who do not respond to oral pharmacotherapy or who cannot use it are good candidates for intracavernosal and intraurethral therapy. Alprostadil is the most widely used drug, both for injection therapy and for the intraurethral route. The efficacy of second-line treatment is high but the attrition rate remains significant.
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In this retrospective analysis of two pivotal trials, vardenafil improved success rates compared with placebo in ED patients who attempted intercourse from as early as 15 minutes or less and through 4-8 hours after dosing in ability to penetrate (SEP2) and from as early as 15 minutes or less and through 8-12 hours after dosing in maintenance of erection (SEP3).
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The underlying mechanism of short-term memory improvement after inhibition of specific phosphodiesterases (PDEs) is still poorly understood. The present study aimed to reveal the ability of PDE5 and PDE2 inhibitors, that increase cyclic guanosine monophosphate (cGMP) and both cyclic adenosine monophosphate (cAMP) and cGMP, respectively, to reverse an object recognition deficit induced by acute tryptophan depletion. Acute tryptophan depletion is a pharmacological challenge tool to lower central serotonin (5-hydroxytryptamine; 5-HT) levels by depleting the availability of its dietary precursor tryptophan. Short-term object memory was tested in male Wistar rats by exposing them to the object recognition task. First, the effects of acute tryptophan depletion upon object recognition 2 h after administration of the nutritional mixture were established. Subsequently, acute tryptophan depletion was combined with the PDE5 inhibitor vardenafil (1, 3 and 10 mg/kg) or with the PDE2 inhibitor BAY 60-7550 (0.3, 1 and 3 mg/kg), 30 min prior to testing. Acute tryptophan depletion significantly lowered plasma tryptophan levels and impaired object recognition performance. Vardenafil (3 and 10 mg/kg) and BAY 60-7550 (3 mg/kg) were able to attenuate the acute tryptophan depletion induced object recognition impairment. Thus, both PDE5 and PDE2 inhibition improved short-term object recognition performance after an acute tryptophan depletion induced deficit. The underlying mechanisms, however, remain poorly understood and further studies are needed to determine whether the present findings can be explained by a direct effect of enhanced cAMP and cGMP levels upon 5-HT activity, or even other neurotransmitter systems, and possibly an interaction with synthesis of nitric oxide or effects upon cerebral blood flow function.
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To assess the efficacy and safety of long-acting injectable testosterone undecanoate (TU, Nebido(®)) in Korean patients with testosterone deficiency syndrome (TDS).
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To assess the efficacy and safety of vardenafil in the treatment of erectile dysfunction (ED) in men of different age groups.
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Erectile dysfunction (ED) affects the sexual lives of millions of men. The first-line oral pharmacotherapy for most ED patients is phosphodiesterase type-5 (PDE-5) inhibitors, of which three are available. Sildenafil is the most widely prescribed oral agent for ED and has a very satisfactory efficacy-safety profile in all patient categories. Tadalafil and vardenafil were introduced in the European Union and in the United States in 2003 and 2004, respectively. The three PDE-5 inhibitors share many pharmacological and clinical characteristics, and each has unique features. This review, which is based on the contemporary literature on PDE-5 inhibitors, describes the chemical, pharmacological, and clinical features of sildenafil, vardenafil, and tadalafil. The first section reviews the pathophysiology of penile erection and PDE-5 inhibitor pharmacology. The second section summarizes data regarding efficacy and safety of the three drugs in treating ED in the general population as well as in selected patient categories.
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In F508del mice, but not in cftr knockout mice, the chloride conductance, evaluated by perfusing the nasal mucosa with a chloride-free solution in the presence of amiloride and with forskolin, was corrected 1 hour after sildenafil administration. A more prolonged effect, persisting for at least 24 hours, was observed with vardenafil. The forskolin response was increased after sildenafil and vardenafil in both normal and F508del mutant animals. In F508del mice, the chloride conductance in the presence of 200 microM 4-4'-diisothiocyanostilbene-2,2'-disulphonic acid, an inhibitor of alternative chloride channels, was much higher after sildenafil injection than after placebo treatment. No effect on the sodium conductance was detected in any group of animals.
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To report experience with combined therapy using intracorporal injection (ICI) of alprostadil and oral phosphodiesterase 5 (PDE-5) inhibitors for the minimally invasive treatment of erectile dysfunction (ED) after radical prostatectomy (RP), as PDE-5 inhibitors are effective but a few patients may have a suboptimal response.
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The study enrolled 46 patients with psychogenic, organic, and mixed ED (20-71 yr of age; IIEF score<26). Patients were randomized to 6 wk of vardenafil, 5 mg/d at bedtime, or placebo.
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Vardenafil is a potent and highly selective oral PDE5 inhibitor. It is effective and generally well tolerated in men with mild to severe ED of varying aetiology, as well as in men with ED associated with diabetes mellitus or ED after radical prostatectomy. Vardenafil should be considered a first-line treatment option in men with ED who are suitable candidates for oral PDE5 inhibitor therapy.