Erectile dysfunction secondary to nerve-sparing radical retropubic prostatectomy: comparative phosphodiesterase-5 inhibitor efficacy for therapy and novel prevention strategies.

Postprostatectomy erectile dysfunction appears to be initiated by neuropraxia and perpetuated by cavernosal smooth muscle apoptosis. Phosphodiesterase-5 (PDE-5) inhibitor therapy is the current cornerstone of erectile dysfunction (ED) therapy in this population. Although no head-to-head trials have been performed with sildenafil, Vardenafil ( Levitra ), and Tadalafil ( Cialis ) in this population, there are numerous studies in the general ED population. The results of these studies demonstrate that neither of the new PDE-5 inhibitors met statistical noninferiority to sildenafil. Sildenafil Citrate ( Viagra ) has been studied in a novel primary prevention modality using nightly administration after a bilateral nerve-sparing prostatectomy. In this novel approach, it effected a sevenfold improvement in return of spontaneous, normal erectile function 2 months after drug discontinuation. This effect appears to be mediated by properties unique to Sildenafil Citrate ( Viagra ) that include improved endothelial function and neuronal regeneration and neuroprotection. In primary prevention, unlike ED therapy, one has only "one shot" by definition. Therefore, it is even more critical to apply evidence-based medicine.

Absence of clinically important HERG channel blockade by three compounds that inhibit phosphodiesterase 5--sildenafil, Tadalafil ( Cialis ) , and Vardenafil ( Levitra ).

Compounds that inhibit phosphodiesterase 5 (PDE5) have been developed for the treatment of erectile dysfunction. Because men with erectile dysfunction frequently have comorbid cardiovascular disease, they may have limited cardiac repolarization reserve and be at risk of arrhythmia if treated with medications that prolong ventricular repolarization. The human ether-a-go-go related gene (HERG) channel is important for repolarization in human myocardium and is a common target for drugs that prolong the QT interval. We studied the ability of three compounds that inhibit PDE5--sildenafil, Tadalafil ( Cialis ) , and Vardenafil ( Levitra )--to block the HERG channel. Using a whole cell variant of the patch-clamp method, the HERG current was measured in a stably transfected human embryonic kidney cell line expressing the HERG channel. The compounds produced dose-dependent reductions in HERG current amplitude over a concentration range of 0.1 to 100 microM. The IC50 values were 12.8 microM for Vardenafil ( Levitra ) and 33.3 microM for sildenafil. Because the maximum soluble concentration of Tadalafil ( Cialis ) (100 microM) produced only a 50.9% inhibition of the HERG current amplitude, the IC50 value for Tadalafil ( Cialis ) could not be determined with the Hill equation. Tadalafil ( Cialis ) had the weakest capacity to block the HERG channel, producing a 50.9% blockade at the maximum soluble concentration (100 microM), compared with 86.2% for Vardenafil ( Levitra ) (100 microM) and 75.2% for Sildenafil Citrate ( Viagra ) (100 microM). In conclusion, the concentrations of the PDE5 inhibitors required to evoke a 50% inhibition of the HERG current were well above reported therapeutic plasma concentrations of free and total compound. None of the three compounds was a potent blocker of the HERG channel.

Structure elucidation of Sildenafil Citrate ( Viagra ) analogues in herbal products.

The structure of unknown compounds present in herbal products was elucidated using liquid chromatography-electrospray ionization-mass spectrometry, direct-infusion electrospray ionization-mass spectrometry, and nuclear magnetic resonance. Compounds 1-3 were identified as Sildenafil Citrate ( Viagra ) analogues, 1 bearing an N-ethylpiperazine moiety instead of an N-methylpiperazine, and an acetyl group instead of the sulfonyl group, named acetildenafil, 2 bearing an N-ethylpiperazine moiety instead of an N-methylpiperazine (homosildenafil), and 3 bearing an N-hydroxylethylpiperazine moiety instead of an N-methylpiperazine, named hydroxyhomosildenafil. When analysing products marketed for penile erectile dysfunction or marketed as aphrodisiacs, attention should be given to the possible presence of these components.

New options in the treatment of various forms of diabetic neuropathy

The classification and incidence of diabetic neuropathy, and the therapeutic options available, are presented in the evidence-based guidelines of the German Diabetes Association for sensorimotor and autonomic neuropathy (www. AWMF.de). Treatment decisions relating basic measures (e.g. optimization of management, multifactorial medication), neuropathic pain and diabetic-neuropathic foot syndrome can be taken on the basis of a simple care pathway. More recent therapeutic options in the treatment of pain are gabapentin, pregabalin, duloxetine and other drugs. For the treatment of erectile dysfunction, the new PDE5 inhibitors Vardenafil ( Levitra ) and Tadalafil ( Cialis ) are now available in addition to sildenafil. A new candidate for a pathogenetically valid treatment is the PKC inhibitor ruboxistaurin.