Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sildenafil citrate is an effective oral drug for erectile dysfunction. The main action of sildenafil is the enhancement of the effect of nitric oxide (NO) by inhibiting the cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase-5 (PDE-5), an enzyme responsible for degradation of cGMP. NO is also present in the nasal mucosa and is responsible for vasodilation causing congestion and nasal obstruction. The aim of this study was to detect the effect of sildenafil on nasal mucosa in terms of nasal obstruction. A total of 16 patients presented to urology clinic suffering from impotence and medicated with sildenafil were included in the study. Before and after oral administration of 50 mg sildenafil, in all of the patients the nasal patency was examined by active anterior rhinomanometry (a method of assessing nasal resistance) using air pressure of 150 Pascal. In addition, all patients were asked about their sensation of nasal patency to detect the symptomatic nasal obstruction. There was a significant decrease in nasal air flow values (cm(3)/s) (p < 0.05). Except for three cases, all patients indicated that they had the sensation of nasal obstruction after the use of sildenafil (p < 0.05). Nasal obstruction is a common complaint for the patients using Sildenafil.
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PMID:Nasal obstruction as a common side-effect of sildenafil citrate. 1649 33

Erectile dysfunction in men with multiple sclerosis (MS) is a very common symptom that often leads to a reduced quality of life. It is related to neurological dysfunction, psychological factors, side effects of medication or generalized MS symptoms, such as fatigue or micturition problems, usually in combination. The question of sexual dysfunction should always be broached during routine follow-up, regardless of age and social status. The possibility that erection problems can be a side-effect of drugs commonly used in MS must also be remembered. There are several effective pharmacological treatments, such as phosphodiesterase inhibitors and prostaglandin E(1) (alprostadil). The contraindications and side effects should be familiar to the MS doctor. Dose titration in the initial stages is recommended to avoid priapism. In the future, combinations of impotence drugs may be tested.
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PMID:Treatment of erectile dysfunction in multiple sclerosis. 1678 15

Phosphodiesterase 5 (PDE5) is one of eleven members of the mammalian phosphodiesterase family that hydrolyzes cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP). Best known as the target of the impotence drug sildenafil, PDE5 degrades cGMP in smooth muscle cells so as to maintain the contracted state of contractile organs such as the penis, blood vessels, uterus, and intestines. In addition, it regulates numerous other physiological processes such as neurogenesis and apoptosis. Like all other PDEs, PDE5 is dimeric; each subunit is approximately 100 kd in size and has two allosteric cGMP-binding sites and a catalytic domain. Protein kinase G (PKG)-mediated phosphorylation and allosteric cGMP binding upregulate PDE5 activity, while PP1 phosphatase-mediated dephosphorylation downregulates. Sildenafil and other selective inhibitors inhibit PDE5 by binding to the catalytic site. From two promoters a single PDE5A gene at human chromosome 4q26 encodes three alternatively spliced isoforms (PDE5A1-3) that differ in the N-terminus. The PDE5A promoter is located upstream of the three isoform-specific first exons (in the order of A1-A3-A2) and consists of a 139-bp core, a 308-bp upstream enhancer, and a 156-bp downstream enhancer. The weaker 182-bp PDE5A2 promoter is located between the A3- and A2-specific exons and contains an indispensable Sp1-binding sequence. Both promoters are responsive to cGMP or cAMP stimulation, and several studies have demonstrated regulation of PDE5 expression possibly through these promoters. Virtually all tissues and cell types express PDE5, with heart and cardiomyocytes being contentious. PDE5A1 and PDE5A2 are ubiquitous, but PDE5A3 is specific to smooth muscle.
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PMID:Expression, distribution and regulation of phosphodiesterase 5. 1701 38

Perception of sexuality varies considerably from population to population and their cultural inheritance, depending on whether you consider occidental, oriental or African cultures. In a wider concept of environment, worries, anxiety or stress induced by work, family, social and economic factors may have a negative impact on sexual functions. Quantitative surveys on sexuality try to measure the incidence of love feelings on sexual behaviour but they cannot determine the close overlaps between mind and body. To give his partner satisfaction, men do not always need performing well. Men also have right to love women, their own ways and according to their means. Impotence or erectile dysfunction (ED) is nowadays a subject that is more and more studied on conceptual, epidemiological as much as clinical levels. Taking this trouble into consideration is relatively new for the general public and seems to coincide with the launching towards the end of the last decade of the first real effective oral treatment, the phosphodiesterase 5 (PDE5) inhibitors and of the communication developed around this event. Demand for sexual problems management seems to be on the increase.
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PMID:[Erectile dysfunction, sexuality and sociocultural aspects]. 1714 47

Assessment and treatment of sexual dysfunction gain more importance in countries like Turkey where cardiovascular events are frequently seen in young adults. The mortality of cardiovascular events is reduced by primary percutaneous coronary angioplasty (PTCA), use of new thrombolytics in acute myocardial infarction (MI), and new drugs used in the treatment of heart failure. Because of the longer life expectancy, assessment of sexual functions and rehabilitation are getting more important in these patients. Since phosphodiesterase type 5 inhibitors (PDE 5) have been frequently utilized in the treatment of impotence, patients' and the doctors' attention have been directed towards cardiovascular risks of sexual activity. In recent years, this topic has become more important because several reports have stated the possible relationship between the use of PDE5 inhibitors and myocardial infarction. It is known, that in patients with cardiovascular diseases, sexual activity poses a low sudden death risk independent of PDE5 inhibitor use. In this review, the points that doctors should take into account while considering and treating the sexual dysfunction in patients with cardiovascular diseases are discussed.
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PMID:[Sexual activity and cardiovascular risk]. 1806 41

Although sildenafil (Viagra) and other phosphodiesterase V (PDE V) inhibitors are increasingly recognized for their use in the treatment of male erectile dysfunction and perhaps more recently pulmonary artery hypertension, less is known of their potential beneficial effects in other situations. Medeiros et al., in the current issue of the British Journal of Pharmacology, report that sildenafil dramatically reduces alcohol-induced gastric damage in rats. The authors provide convincing evidence that such protection not only occurs via the nitric oxide (NO)/cGMP pathway, but also involves regulation of ATP-sensitive potassium channels. Therefore, in addition to exerting anti-impotence efficacy, PDE V inhibitors may provide significant beneficial effects from mucosal injury induced by alcohol.
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PMID:Sildenafil reduces alcohol-induced gastric damage: just say 'NO'. 1807

Cardiovascular diseases like hypertension, hyperlipidemia, diabetes mellitus and obesity are the important predictors of erectile dysfunction (ED). Endothelial dysfunction is proposed to be the underlying cause of ED, just like coronary artery disease. Sildenafil was originally developed to treat angina pectoris but later on was recognized as novel treatment option for impotence. To date, sildenafil has been the most extensively studied PDE (phosphodiesterase)-5 inhibitor. Currently two more PDE-5 inhibitors, tadalafil and vardenafil, are under study. Newer compounds have certain advantages over sildenafil, including greater selectivity for PDE-5 compared with other isoenzymes, absence of effect of food on absorption, faster onset and longer duration of action. PDE-5 inhibitors are emerging as novel therapeutic tools with a potential to protect or enhance endothelial function in humans and to selectively improve regional blood flow. The FDA has recently approved a reformulation of sildenafil for the treatment of pulmonary arterial hypertension. Raynaud's phenomenon, respiratory disorders with ventilation/ perfusion mismatch, congestive cardiac failure, hypertension and stroke are the other conditions in which PDE-5 inhibitors are being tried. It is hoped that this group of drugs will soon emerge as a novel weapon in the armamentarium against various cardiovascular and pulmonary diseases.
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PMID:Novel phosphodiesterase-5 inhibitors: current indications and future directions. 1817 38

To identify the active substance in the male silkworm pupae that strengthens men's vitality, the vasorelaxation activity was determined by measuring the vascular endothelial nitric oxide (eNO) produced in calf pulmonary artery endothelial (CPAE) cells treated with extracts from the pupae. Dried silkworm male pupae were extracted with ethanol and suspended in water, then partitioned with hexane, chloroform, ethylacetate, and butanol, sequentially. Among these fractions, the aqueous fraction had maximal NO production (156.87 microM/200 microl well, 10 mg/ml) and minimal cytotoxicity (IC50 362.3 mg/ml). The vasorelaxation substances (VAS) from the aqueous fraction were isolated by a combination of gel filtration and anion-exchange chromatography on DEAE Sephadex A-25 and reverse phase-HPLC. Their chemical structures were determined on the basis of their spectroscopic parameters of EI-MS, MALDI-TOF MS, 1H and 13C NMR, 1H-1H COSY, and GC-MS spectral data. The active substance was subsequently identified as a dimethyladenosine and dimethyladenosine-5'-L-arabinose that has phosphodiesterase (PDE) inhibition activity. This compound was shown to inhibit PDE4 activity in a dose-dependent manner. Also, it inhibited the PDE5 activity of cyclic-GMP-specific PDE5 enzyme. These results imply that dimethyladenosine may be a lead compound for the development and improvement of vasculogenic impotence drugs through phosphodiesterase inhibition and NO production in endothelial cells.
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PMID:Purification of a dimethyladenosine compound from silkworm pupae as a vasorelaxation substance. 1833 35

Plant extracts traditionally used for male impotence (Tribulus terrestris, Ferula hermonis, Epimedium brevicornum, Cinnamomum cassia), and the individual compounds cinnamaldehyde, ferutinin, and icariin, were screened against phosphodiesterase-5A1 (PDE5A1) activity. Human recombinant PDE5A1 was used as the enzyme source. Only E. brevicornum extract (80% inhibition at 50 microg/mL) and its active principle icariin (1) (IC50 5.9 microM) were active. To improve its inhibitory activity, 1 was subjected to various structural modifications. Thus, 3,7-bis(2-hydroxyethyl)icaritin (5), where both sugars in 1 were replaced with hydroxyethyl residues, potently inhibited PDE5A1 with an IC50 very close to that of sildenafil (IC50 75 vs 74 nM). Thus, 5 was 80 times more potent than 1, and its selectivity versus phosphodiesterase-6 (PDE6) and cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) was much higher in comparison with sildenafil. The improved pharmacodynamic profile and lack of cytotoxicity on human fibroblasts make compound 5 a promising candidate for further development.
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PMID:Potent inhibition of human phosphodiesterase-5 by icariin derivatives. 1877 98

Impotence is one of the common complications after the radical prostatectomy. One of the main reasons of this complication is due to the dysfunction of the veins in corpus cavernosum. Recent studies have shown that the erectile function is improved after the long-term therapy of phosphodiesterase type 5 inhibitor among patients with post-prostatectomy erectile dysfunction. In this study, we evaluated the effects of mirodenafil on the penile erection and corpus cavernosum tissues in the rat model of cavernosal nerve injury. Rats were divided into four groups: (1) control group, (2) bilateral cavernosal nerve injury group, (3) mirodenafil 10 mg therapy group after the nerve injury and (4) mirodenafil 20 mg therapy group after the nerve injury. After we identified the nerve from the pelvic nerve complex on the lateral side of the prostate, the rats in the control group were sutured without causing any nerve injury and in other groups we damaged the nerve by compressing it with a vessel clamp. Then, 10 and 20 mg kg(-1) of mirodenafil were orally administered to two experimental groups. After 8 weeks, the intracavernosal pressure (ICP) was recorded. The immunohistochemical staining and western blot were performed, and the effect of mirodenafil on the expression of cyclic guanosine monophosphate (cGMP) was evaluated through enzyme-linked immunosorbent assay. The ICP of nerve-injured group was decreased compared with the control group; however, the ICP of the mirodenafil-administered groups was improved compared with the nerve-injured group. The Masson's trichrome staining confirmed that the smooth muscle (SM) component was increased in the mirodenafil-administered groups. The nitric oxide synthase expression and cGMP of mirodenafil-administered groups was increased compared with the nerve-injured group. Long-term therapy of mirodenafil may improve the erectile function after the radical prostatectomy by preserving the SM content and inhibiting the fibrosis of the corpus cavernosum.
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PMID:The effect of mirodenafil on the penile erection and corpus cavernosum in the rat model of cavernosal nerve injury. 2086 45


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