Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three different phosphodiesterase 5 (PDE5) inhibitors are currently available for the treatment of erectile dysfunction: sildenafil, vardenafil and tadalafil. The differences between these 3 are limited: tadalafil has a long duration of action, while vardenafil has a rapid onset of action after intake. Various studies have suggested that there is an improvement in the partners' sex lives when men use a PDE5 inhibitor for erectile dysfunction. The introduction of PDE5 inhibitors has renewed the interest in PDE inhibitors in general, for example in the treatment of pulmonary hypertension. In the near future PDE inhibitors may be used for various disorders as chronic obstructive pulmonary disease, benign prostatic hyperplasia, hypertension and coronary heart disease.
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PMID:[Phosphodiesterase inhibitors: effectiveness and new applications]. 1690 Oct 64

During many years, the symptom of erectile dysfunction was a matter for the urologist or the sexologist without efficacious treatment. Since 1999, the unexpected efficacy of sildenafil initially tested as a coronary vasodilatator emphasized the major role of an endothelial dysfunction potentially corrected by type 5 phosphodiesterase inhibitors (5-PDEI), which are able to reinforce the NO-dependant vasodilatation of cavernous arteries. Due to the medicalisation and the mediatisation of erectile dysfunction during the past five years, this symptom is now a matter for the cardiologist. The first reason was the query of cardiovascular safety of 5-PDEI. American and Britannic registries have established a good cardiovascular tolerability of these drugs including in patients with coronary heart disease according to the respect of contraindication in cases of coprescription with nitrates. The second was the association of erectile dysfunction with many cardiovascular risk factors concerned by the cardiologist. The third reason was the observation that erectile dysfunction could be a potential marker to identify patients with silent myocardial ischemia and relevant coronary artery disease. The Princeton consensus provides guidelines to help the cardiologist in the evaluation of patients with erectile dysfunction according to the cardiovascular risk level. Henceforth, erectile dysfunction should be considered by the cardiologist as "a sound of silence" of myocardial ischemia and should encourage to more aggressive evaluation and treatment of cardiovascular risk factors.
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PMID:[Erectile dysfunction, a new symptom for the cardiologist]. 1692 67

Our rapidly expanding knowledge regarding the biology of the endothelial cell and the pathophysiology of coronary heart disease (CHD) and endothelial dysfunction indicates important common factors and overlapping clinical presentations. We are, in effect, presented with a new paradigm-that of varying vascular manifestations of disease linked to the functioning of endothelial cell lining. This article reviews these areas of advancement and addresses their clinical implications regarding erectile dysfunction and CHD, as well as the role of the phosphodiesterase-5 inhibitor sildenafil.
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PMID:Endothelial dysfunction, erectile dysfunction, and coronary heart disease: the pathophysiologic and clinical linkage. 1698 79

Since the discovery of sildenafil in 1989 as a highly selective inhibitor of the phosphodiesterase type-5 (PDE-5) receptor, 2 additional PDE-5 inhibitors, tadalafil and vardenafil, have emerged as safe and effective treatments of erectile dysfunction (ED). Enzymes in the PDE family catalyze the hydrolysis of the intracellular signaling molecules cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which is the second messenger of nitric oxide (NO) and a principal mediator of smooth muscle relaxation and vasodilation. Sildenafil was initially introduced for clinical use as the result of extensive research on chemical agents targeting PDE-5 that might potentially be useful in the treatment of coronary heart disease. Erection is largely a hemodynamic event, which is regulated by vascular tone and blood flow balance in the penis. Endothelial dysfunction, an early component of atherosclerosis, may inhibit a vascular event such as erection and is rarely confined to the arteries supplying blood to the penis, but more likely occurs throughout the vascular bed. In addition to the effects of the NO-cGMP signaling pathway on cavernosal smooth muscle, clinical findings have suggested that vascular tone in the pulmonary, coronary, and other vascular tissues expressed by PDE-5 is also influenced by this signal transduction mechanism. This has led to the emergence of novel therapeutic indications for sildenafil over a range of cardiovascular conditions that are either well-established risk factors or comorbidities with ED. Recently, the U.S. Food and Drug Administration approved sildenafil as an orally active therapy for the treatment of primary pulmonary hypertension. The drug will be marketed under the trade name of Revatio, not Viagra, the name used for the ED indication. The approved dose for primary pulmonary hypertension is 20 mg 3 times daily.
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PMID:Type 5 phosphodiesterase inhibitors in the treatment of erectile dysfunction and cardiovascular disease. 1730 94

Cerebral ischemia resulting from transient or permanent cerebral artery occlusion leads to neuronal cell death, and eventually causes neurological impairments. Tadalafil (Cialis)is a long-acting phosphodiesterase type-5 (PDE-5) inhibitor used to treat erectile dysfunction. The therapeutic effects of PDE-5 inhibitors on chronic obstructive pulmonary disease, prostate hyperplasia, hypertension, and coronary heart disease have been reported. The present study investigated the effects of tadalafil on short-term memory, cyclic guanosine monophosphate (cGMP) level, apoptotic neuronal cell death, and cell proliferation in the hippocampus following transient global ischemia in gerbils. For this study, a step-down avoidance task, cGMP assay, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and immunohistochemistry for caspase-3 and 5-bromo-2'-deoxyuridine were performed. The results revealed that ischemic injury increased apoptotic neuronal cell death in the hippocampal CA1 region, impaired short-term memory, and decreased cGMP level. Ischemic injury enhanced cell proliferation in the hippocampal dentate gyrus. Tadalafil treatment improved short-term memory by suppressing ischemia-induced apoptotic neuronal cell death in the hippocampal CA1 region, and decreased cGMP level. Also, tadalafil suppressed the ischemia-induced increase in cell proliferation in the hippocampal dentate gyrus. We showed that tadalafil can overcome ischemia-induced apoptotic neuronal cell death, thus facilitates recovery following ischemic cerebral injury.
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PMID:Tadalafil improves short-term memory by suppressing ischemia-induced apoptosis of hippocampal neuronal cells in gerbils. 1901 Mar 46

Though antiplatelet drugs are proven beneficial to patients with coronary heart disease and stroke, more effective and safer antiplatelet drugs are still needed. In this study we report the antiplatelet effects and mechanism of BF0801, a novel adenine derivative. BF0801 dramatically inhibited platelet aggregation and ATP release induced by ADP, 2MeSADP, AYPGKF, SFLLRN or convulxin without affecting shape change in vitro . It also potentiated the inhibitory effects of adenosine-based P2Y12 antagonist AR-C69931MX or phosphodiesterase (PDE) inhibitor IBMX on platelet aggregation. The cAMP levels in both resting and forskolin-stimulated platelets were increased by BF0801 suggesting its PDE inhibitor activity, which is further confirmed by the concentration-dependent suppression of BF0801 on the native and recombinant PDE. Similar to AR-C69931MX, BF0801 drastically inhibited 2MeSADP- induced adenylyl cyclase inhibition in platelets indicating its P2Y12 antagonism activity, which is substantiated by the inhibition of BF0801 on the interaction between ADP and P2Y12 receptor expressed in CHO-K1 cells measured by atomic force microscopy. Moreover, we confirmed the antiplatelet effects of BF0801 using platelets from rats intravenously given BF0801. In summary, for the first time we developed a novel adenine derivative bearing dual activities of PDE inhibition and P2Y12 antagonism, which may have therapeutic advantage as a potential antithrombotic drug.
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PMID:BF0801, a novel adenine derivative, inhibits platelet activation via phosphodiesterase inhibition and P2Y12 antagonism. 2080 21

The enzyme phosphodiesterase-5 (PDE-5), widely distributed in the heart, smooth muscle, and blood vessels, catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator, and is also a nitric oxide (NO) donor. Tadalafil is the first PDE 5 inhibitor approved by FDA for the treatment of ED. Recent studies have shown several pleiotropic beneficial effects of PDE-5 inhibitors in patients with cardiovascular diseases (coronary heart disease, hypertension, heart failure, and pulmonary arterial hypertension) and diabetes mellitus. It has been demonstrated that tadalafil can not only improve sexual function, but also elevate the endothelial cell-derived NO level, activate protein kinase A, upregulate the intracellular Ca2+ concentration, and improve hemodynamic indexes. Thus, the PDE-5 inhibitor tadalafil, with its cardiovascular-protective effect, can be a therapeutic option for the treatment of ED patients with cardiovascular disease.
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PMID:[Cardiovascular-protective effect of tadalafil in the treatment of erectile dysfunction]. 2443 31

Methyloxantines are present in many herbs and vegetal foods, among them in tea, coffee and chocolate. Previous studies revealed that theophylline and theobromine have anti-angiogenic properties. Anti-tumor properties of theobromine were also described. Pentoxifylline (3,7-dimethyl-1-(5-oxohexyl)xanthine, PTX) is a synthetic xanthine derivative. It is a phosphodiesterase inhibitor and has various anti-inflammatory abilities. Pentoxifylline is widely used in therapy of inflammatory arterial diseases such as intermittent claudication of upper and lower limbs as well as in coronary heart disease. The aim of our research was to evaluate the effect of pentoxifylline (individually and in combination with non-steroidal anti-inflammatory drug sulindac), on L-1 sarcoma angiogenic activity and tumor formation in syngeneic Balb/c mice. Pre-incubation of tumor cells for 90 min with various PTX concentrations resulted in dose-dependent decrease of their ability to induce newly-formed blood vessels after transplantation into the skin of recipient mice. Administration of PTX to mice, recipients of tumor cells, slows tumor growth and reduces its volume. Synergistic inhibitory effect of PTX and sulindac, expressed as % of tumors sixth and thirteen day after subcutaneous grafting of L-1 sarcoma into syngeneic Balb/c mice, was observed.
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PMID:The effect of pentoxifylline on L-1 sarcoma tumor growth and angiogenesis in Balb/c mice. 2886 Sep 31


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