Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphodiesterases (PDEs) are a superfamily of enzymes that degrade the intracellular second messengers cyclic AMP and cyclic GMP. As essential regulators of cyclic nucleotide signalling with diverse physiological functions, PDEs are drug targets for the treatment of various diseases, including heart failure, depression, asthma, inflammation and erectile dysfunction. Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. It is well known as the target of sildenafil citrate (Viagra) and other similar drugs for the treatment of erectile dysfunction. Despite the pressing need to develop selective PDE inhibitors as therapeutic drugs, only the cAMP-specific PDE4 structures are currently available. Here we present the three-dimensional structures of the catalytic domain (residues 537-860) of human PDE5 complexed with the three drug molecules sildenafil, tadalafil (Cialis) and vardenafil (Levitra). These structures will provide opportunities to design potent and selective PDE inhibitors with improved pharmacological profiles.
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PMID:Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules. 1295 49

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

This paper reviewed the efficacy and safety of vardenafil, a highly selective phosphodiesterase type 5 (PDE 5) inhibitor, in men with erectile dysfunction who were difficult to treat. Several large-scale studies indicated vardenafil was effective and safe in the treatment of these difficult-to-treat ED patients, including ED with depression or diabetes, ED after radical retropubic prostatectomy, ED caused by spinal cord injury, and sildenafil nonresponders. Vardenafil provides a rational treatment alternative.
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PMID:[Efficacy and safety of vardenafil in difficult-to-treat erectile dysfunction men]. 1668 77

In recent years, more and more attention has been drawn to the role of phosphodiesterase 5 (PDE5) in penile erection. The cyclic nucleotide (cGMP) signaling pathway mediates the smooth-muscle relaxing effect of nitric oxide necessary for normal erectile function. Down-regulation of this pathway is the pathological pivot of many forms of erectile dysfunction (ED) and leads to the development of some chronic diseases. Therapeutic outcomes have shown that vardenafil is effective and safe in the treatment of ED associated with dyslipidemia, hypertension, depression, diabetes, radical retropubic prostatectomy, spinal cord injury, sildenafil failure, renal transplantation, chronic prostatitis and that accompanied by premature ejaculation. Vardenafil provides a reasonable therapeutic alternative for these refractory ED patients. In addition, vardenafil can prolong erectile duration of ED patients.
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PMID:[Vardenafil for refractory erectile dysfunction: the latest advances]. 2021 19