The increasing rate of cardiovascular disorders contributes to rising hospitalized patients receive chronic oral beta-blocker therapy. Beta-blockers remain one the fundamental therapy for heart failure. Still, their role in decompensated failure and severe sepsis during hospitalization is often debated inconsistent clinical practice. In recent years, evidence efficacy outcomes beta-blockers acu...

For years, phosphodiesterase type 5 inhibitors have been used for the treatment of erectile dysfunctions. Due to the similarities between male and female sexual response, several studies have assessed the effects of sildenafil citrate (Viagra(®)) in women affected by female sexual arousal disorder. The results are still conflicting and the drug is not devoid of adverse effects. Furthermore, fem...

The objective of this study was to identify the use of phosphodiesterase type 5 inhibitors among university students from the city of Sao Paulo (SP) in Brazil. Male students (n=350) replied to a questionnaire about diagnosis of erectile dysfunction, the frequency and reason for the use of phosphodiesterase type 5 inhibitors, the specific medication used, whether their use was accompanied by a m...

A strong and independent association between lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) and erectile dysfunction (ED) has been widely evidenced in several clinical epidemiologic studies. Preclinical animal models have provided a great deal of information on potential common pathogenic mechanisms underlying these two clinical identities. Although the effic...

The aim of the present study was to investigate the relaxant effects of selective III, IV and nonselective phosphodiesterase inhibitors, e.g. amrinone, rolipram and theophylline, respectively, on isolated tracheal preparations in streptozotocin (STZ)-diabetic rats. Six weeks before the experiments, the rats to be made diabetic were anesthetized with diethyl ether and diabetes was then induced b...

The type V cyclic GMP phosphodiesterase was partially purified from the high-speed supernatant of guinea-pig lung. The isoenzyme displayed linear kinetics for cyclic GMP hydrolysis, with Km = 2.2 ± 0.2 ,tM and Vmax = 1.2 ± 0.08 nmol/ min per mg. The selective type V phosphodiesterase inhibitor Zaprinast inhibited cyclic GMP hydrolysis with IC50 (concn. giving 50% inhibition) = 0.45 + 0.08 /,M. ...

Background— cGMP phosphodiesterase type 5 protein is upregulated in myocardial hypertrophy. However, it has never been ascertained whether phosphodiesterase type 5 inhibition exerts an antiremodeling effect in nonischemic heart disease in humans. We explored the cardioreparative properties of a selective phosphodiesterase type 5 inhibitor, sildenafil, in a model of diabetic cardiomyopathy. Meth...

I agree with A.H. Morice and coworkers that the relatively short half-life of sildenafil (3–4 h) may be a drawback of this drug. Patients’ compliance may rarely be an issue. However, the fluctuations in sildenafil plasma concentrations are poorly tolerated by some patients. A drug with a much longer halflife, such as tadalafil (,18 h), might be advantageous, but caution is necessary. GHOFRANI e...

The treatment modalities of erectile dysfunction range from oral pharmacotherapy to intracavernosal injections, intraurethral pellets, vacuum erectile devices, and the surgical option of penile prosthesis insertion. Oral phosphodiesterase 5 inhibitors still remain the preferred treatment for patients since they are the least invasive, not to mention that they can be prescribed by non-urologists...

In this Letter we describe our ongoing target repurposing efforts focused on discovery of inhibitors of the essential trypanosomal phosphodiesterase TbrPDEB1. This enzyme has been implicated in virulence of Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). We outline the synthesis and biological evaluation of analogs of tadalafil, a human PDE5 inhibitor currently u...