Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erectile dysfunction (ED) tends to be associated with other diseases, the common basis of which is endothelial dysfunction. ED is also frequently combined with LUTS and the common basis for both conditions seems to be elevation of Rho-kinase activity and decrease of NO concentration. Because all three PDE 5 inhibitors sildenafil, tadalafil, and vardenafil have a common mode of action, i.e., inhibition of PDE 5, they are not different in terms of their efficacy and safety profile except for color vision disturbances which are more common after sildenafil and back pain/myalgia more often observed after tadalafil. The main differentiating characteristics among the three PDE 5 inhibitors are their pharmacokinetics. These are ultimately responsible for the observation that in head-to-head comparative trials depending on the respective study design the overwhelming majority of the patients opted either for tadalafil as the longest acting PDE 5 inhibitor (36 h) or for vardenafil as a relatively rapidly acting drug. All published studies so far have shown that in terms of the cardiovascular risk profile (myocardial infarction rate) all three PDE 5 inhibitors performed better than placebo although the results were not statistically significant. Without any exception it applies to all three PDE 5 inhibitors that they are absolutely contraindicated in patients taking nitrate- or molsidomine-containing medications and that they may interact in particular with non-uroselective alpha-adrenoceptor blockers. This is why their simultaneous application with PDE 5 inhibitors has to be avoided.In the near future chronic (daily) application of a PDE 5 inhibitor may show advantages, at least in those 50-60% of all patients in whom there is a high likelihood of endothelial dysfunction due to the diagnostic (penile duplex Doppler) outcome. Possible new developments in the management of ED with a time frame of 5-8 years until their market approval are guanylate cyclase activators, Rho-kinase inhibitors, melanocortin receptor agonists, gene therapy, and tissue engineering.
 ...
PMID:[Erectile dysfunction. New drugs with special consideration of the PDE 5 inhibitors]. 1519 47

The treatment of erectile dysfunction (ED) has been revolutionized during the last 2 decades with several treatment options now available. Most of these treatments are associated with high efficacy rates and favourable safety profiles. A MEDLINE search was undertaken to evaluate all currently available data on treatment modalities for ED. Phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, vardenafil) are currently the first-choice treatment option for ED by most physicians and patients. In addition, several new PDE5 inhibitors are candidates to enter the market in forthcoming years (avanafil, udenafil, SLx-2101, mirodenafil [SK3530]). However, obvious pharmacokinetic differences that result in a faster time-to-onset, longer half-life time and better safety profile are required for these drugs to be considered a truly better option for patients. Other molecules in development include selective dopamine, glutamate, serotonin and melanocortin receptor agonists, guanylate cyclase activators, rho-kinase inhibitors and hexarelin analogues, while the first trials on gene therapy and tissue engineering for reconstruction of corporal tissue are under way. Patients must be aware of all treatment options since no ideal treatment exists. It is expected that the availability of drugs with different mechanisms of action will allow physicians to offer more personalized medicine to their patients in the future. The development and adaptation of a patient-centred care model in sexual medicine will increase the efficacy and safety of current and future treatments.
 ...
PMID:Looking to the future for erectile dysfunction therapies. 1819 27