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Topic: PDE5

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	tBLOG - PDE5
		PDE5 activity is modulated by a rapidly reversible redox switch.
		Chemical reduction of PDE5 relieves autoinhibition of enzyme functions; allosteric cGMP-binding activity is increased 10-fold, and catalytic activity is increased ~3-fold.
		A change in the state of reduction of PDE5 or the isolated regulatory domain is associated with an apparent conformational change similar to that caused by phosphorylation.
	pde5.tblog.com (134 words)

	Patient Care - How to choose among the PDE5 inhibitors for erectile dysfunction (Site not responding. Last check: 2007-11-04)
		Phosphodiesterase 5 (PDE5) inhibitors are both efficacious and easy to use, so most cases of ED are no longer treated by the urologist: Approximately two thirds of prescriptions for sildenafil (Viagra) in 2002 were written by primary care physicians.
		All PDE5 inhibitors are absolutely contraindicated in persons who take organic nitrates, and some clinicians will not prescribe a PDE5 inhibitor to a man who has nitrates at home, even if he maintains that he has not used them for a long time.
		If PDE5 inhibitors are demonstrated in the future to differ from one another significantly in some experiential fashion, patients may elect to use more than 1 agent from the class, though the concomitant administration of more than one would not make pharmacologic sense.
	www.patientcareonline.com /patcare/article/articleDetail.jsp?id=112796 (3103 words)

	Sexual Dysfunction in Men
		Vardenafil is a phosphodiesterase type 5 (PDE5) inhibitor with a pharmacokinetic profile and molecular configuration nearly identical to that of sildenafil.
		To help select the most appropriate PDE5 inhibitor for patients with ED, and in the absence of carefully controlled, published head-to-head trials, it is important to examine some of the distinguishing characteristics of these agents, including selectivity, onset and duration of action, and safety and efficacy.
		In addition to inhibiting PDE5, both sildenafil and vardenafil also produce modest PDE6 effects at the upper limits of the dosage range, whereas these effects are absent with tadalafil.
	www.bumc.bu.edu /Dept/Content.aspx?DepartmentID=371&PageID=7640 (1588 words)

	CLINICAL PHARMACOLOGY Mechanism of Action - Meltabs \| Meltabs Description Generic Viagra (Site not responding. Last check: 2007-11-04)
		In addition to human corpus cavernosum smooth muscle, PDE5 is also found in lower concentrations in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle.
		The inhibition of PDE5 in these tissues by sildenafil (Meltabs) may be the basis for the enhanced platelet antiaggregatory activity of nitric oxide observed in vitro, an inhibition of platelet thrombus formation in vivo and peripheral arterial-venous dilatation in vivo.
		Sildenafil (Meltabs) is only about 10-fold as potent for PDE5 compared to PDE6, an enzyme found in the retina which is involved in the phototransduction pathway of the retina.
	www.buy-softtabs.com /meltabs-desc/meltabs-desc-9.html (327 words)

	Men's Health of Palm Beach Newsletter, July 2003
		With PDE5 inhibitors that have a duration of action of approximately 4 hours (Viagra and Levitra), the need to modify sexual patterns to take advantage of the drug's period of efficacy may be an obstacle to effective therapy and resumption of normal sexual activity.
		PDE5 inhibitor therapy has been found to be safe in most patients including those with CVD and those receiving standard antihypertensive agents.
		Overall, the current and new PDE5 inhibitors generally produce mild vasodilation and minimal effects on blood pressure, and are not associated with increased risk of MI or death rates.
	www.menshealthfl.com /newsletters/0308.htm (1794 words)

	Mode of action
		However, its selectively is only 10-fold as potent for PDE5 compared to PDE6 (found in the retina) which could be the basis for abnormalities related to colour vision (blue, green) which have been talked about a lot in the media.
		PDE5 is also found in lower concentrations in the platelets, vascular and visceral smooth muscle and skeletal muscle.
		Sildenafil inhibits PDE5 in these tissues as well, which is the cause of several side effects which are believed to be due to Viagra.
	www.ch.ic.ac.uk /local/projects/p_hazel/mode2.html (724 words)

	Viagra - Viagra Side Effects - Viagra Information - Canadian Pharmacy
		Sildenafil is about 10-fold as potent for PDE5 compared to PDE6, an isoenzyme found in the retina; this lower selectivity is thought to be the basis for color vision abnormalities observed with higher doses or plasma levels of sildenafil (see Precautions).
		PDE5 is also found in lower concentrations in platelets, vascular and visceral smooth muscles, and skeletal muscle.
		The sildenafil-induced inhibition of PDE5 in these tissues appears to be the basis for the enhanced platelet antiaggregatory activity of nitric oxide observed in vitro, and inhibition of platelet thrombus formation in vivo, and peripheral arterial-venous dilation in vivo (see Precautions).
	www.rxcanadapharmacy.com /htmfiles/Viagra.asp (3731 words)

	Viagra Pharmacology, Pharmacokinetics, Studies, Metabolism - Sildenafil Citrate - RxList Monographs
		The approximately 4000-fold selectivity for PDE5 versus PDE3 is important because that PDE is involved in control of cardiac contractility.
		Sildenafil is only about 10-fold as potent for PDE5 compared to PDE6, an enzyme found in the retina; this lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or plasma levels (see Pharmacodynamics).
		The inhibition of PDE5 in these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of nitric oxide observed in vitro, an inhibition of platelet thrombus formation in vivo and peripheral arterial-venous dilatation in vivo.
	www.rxlist.com /cgi/generic/viagra_cp.htm (2520 words)

	Developmental Changes in Lung cGMP Phosphodiesterase-5 Activity, Protein, and Message -- HANSON et al. 158 (1): 279 -- ...
		PDE5 activity was determined by the difference in activity of the enzyme in the presence and absence of 4 µM zaprinast.
		In the immunoblot containing the soluble fractions, the fetal PDE5 protein is increased, with a decrease observed by 10 min and lasting until the secondary rise, observed at 7 d.
		PDE5 activity in the supernatant decreases 2-fold within 1 h after delivery in normal fetuses, as seen in Figures 2 and 3.
	ajrccm.atsjournals.org /cgi/content/full/158/1/279 (6924 words)

	PDE5A - cGMP-specific 3',5'-cyclic phosphodiesterase
		Double immunostaining of PDE2, PDE5, or PDE9 mRNAs with the neuronal marker NeuN and the glial cell marker glial fibrillary acidic protein revealed that these mRNAs were predominantly expressed in neuronal cell bodies.
		Two novel PDE5 inhibitors, tadalafil (Lilly ICOS) and vardenafil (Bayer), have recently completed efficacy and safety clinical trials in 'general' and diabetic study populations and are now candidates for US FDA approval.
		Increased activity of PDE5 (and perhaps also PDE9) in glomeruli and in cells of collecting ducts in sodium-retaining states, such as nephrotic syndrome, accounts for renal resistance to atriopeptin; diminished ability to excrete sodium can be corrected by administration of the selective PDE5 inhibitor zaprinast.
	www.pdg.cnb.uam.es /UniPub/iHOP/gg/94030.html (2067 words)

	Cyclic GMP Phosphodiesterases and Regulation of Smooth Muscle Function -- Rybalkin et al. 93 (4): 280 -- Circulation ...
		PDE5 activity was expressed as percent of control, and control (nonstimulated) PDE5 activity was defined as 100%.
		PDE5 is converted to an activated state upon cGMP binding to the GAF A domain.
		PDE5 is converted into an activated state after binding of cGMP to the GAF A domain.
	circres.ahajournals.org /cgi/content/full/93/4/280 (8036 words)

	Cialis (tadalafil) - Cialis Dosing, Cialis side effects * not an advertisement
		(PDE5 is not the only phosphodiesterase involved in the erectile physiology but it appears to be the most important one).
		The nice thing about PDE5 blockers is that they shouldn't cause erections at inappropriate times because they only block degradation of cGMP produced in reaction to sexual stimulation, such as thinking about something sexy.
		If you are going to take any of the PDE5 inhibitors such as Cialis, it is very important that your doctor be aware if you have a liver condition (such as cirrhosis) or kidney condition (such as if you are on dialysis) because you may need a special dosage adjustment.
	www.coreynahman.com /cialis.html (1553 words)

	Inhouse Pharmacy CIALIS prices
		PDE5 is an enzyme found in corpus cavernosum smooth muscle, vascular and visceral smooth muscle, skeletal muscle, platelets, kidney, lung, and cerebellum.
		This selectivity for PDE5 over PDE3 is important because PDE3 is an enzyme involved in cardiac contractility.
		Additionally, tadalafil is approximately 700-fold more potent for PDE5 than for PDE6, an enzyme which is found in the retina and is responsible for phototransduction.
	www.inhousepharmacy.com /mens-health/cialis-information.html (2838 words)

	Regulation of cGMP-specific Phosphodiesterase (PDE5) Phosphorylation in Smooth Muscle Cells -- Rybalkin et al. 277 (5): ...
		PDE5 was detected using a C-terminal polyclonal PDE5 antibody.
		Activation of PKG in mouse uterus causes significant phosphorylation of PDE5.
		The Role of PKG Phosphorylation of PDE5 in Smooth Muscle-- The physiological function for the phosphorylation and activation of PDE5 is not yet established.
	www.jbc.org /cgi/content/full/277/5/3310 (6691 words)

	cilais (Site not responding. Last check: 2007-11-04)
		Because sexua stimulatio is required to initiate the local releas of nitric oxide, the inhibitio of PDE5 by tadalafil has no effec in the absenc of sexua stimulation.
		PDE5 is found in corpu cavernosum smooth muscle, vascula and viscera smooth muscle, skeleta muscle, platelets, kidney, lung, cerebellum, and pancreas.
		Additionally, tadalafil is 700-fold more poten for PDE5 than for PDE6, which is found in the retin and is responsible for phototransduction.
	www.cialis.cialis.tourneo.ro (8585 words)

	Icariin : by Ray Sahelian, M.D., icariin for erectile function
		METHODS: PDE5 was isolated from the human platelet and PDE4 from the rat liver tissue.
		The IC(50) of Icariin and papaverine on PDE5 were 0.432 micromol/L and 0.680 micromol/L, respectively and those on PDE4, 73.50 micromol/L and 3.07 micromol/L, respectively.
		The inhibitory effects of icariin on PDE5 and PDE4 activities were investigated by the two-step radioisotope procedure.
	www.raysahelian.com /icariin.html (635 words)

	The effect of PDE5 inhibition on patients with stable angina
		Furthermore, in patients with coronary heart disease, coronary flow reserve and coronary artery endothelial function improved after the administration of sildenafil and PDE5 inhibitors may therefore be of use in improving the performance of angina patients.
		Vardenafil did not impair the ability of patients with coronary artery disease to exercise at levels equivalent or greater than that attained during sexual intercourse suggesting that vardenafil may be of use in treating patients with concomitant angina and erectile dysfunction.
		Furthermore these data add support the concept that PDE5 inhibitors may be of use in the treatment of coronary artery disease although data showing that PDE5 inhibitors may be detrimental in patients at risk of heart failure should be considered in this respect.
	www.bioportfolio.com /LeadDiscovery/PubMed-010302.html (838 words)

	Cialis (Site not responding. Last check: 2007-11-04)
		Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 by tadalafil has no effect in the absence of sexual stimulation.
		PDE5 is found in corpus cavernosum smooth muscle, vascular and visceral smooth muscle, skeletal muscle, platelets, kidney, lung, cerebellum, and pancreas.
		Additionally, tadalafil is 700-fold more potent for PDE5 than for PDE6, which is found in the retina and is responsible for phototransduction.
	www.panopharma.com /cialis.htm (664 words)

	Individual Cerebellar Purkinje Cells Express Different cGMP Phosphodiesterases (PDEs): In Vivo Phosphorylation of ...
		PDE5 is expressed in the entire Purkinje cell layer (A), whereas PDE1B is expressed in subsets of Purkinje neurons (B).
		PDE5 activity was calculated as a percentage of control (untreated slices).
		of PDE1B and PDE5 in mouse cerebellar Purkinje neurons (Fig.
	www.jneurosci.org /cgi/content/full/23/16/6452 (4876 words)

	Targeting PDE5 for the treatment of pulmonary hypertension
		NO has been implicated in the cause and treatment of pulmonary hypertension and since PDE5 is expressed in the human pulmonary artery this condition is emerging as a possible new indication for PDE5 inhibitors (see "Phosphodiesterase 4 (PDE4) and Phosphodiesterase 5 (PDE5): Pharmaceutical advances and new therapeutic targets" click here for access).
		Early clinical studies demonstrated that sildenafil was able to decrease mean pulmonary arterial pressure in patients with primary pulmonary hypertension alone and, furthermore it also increased the efficacy of iloprost, one of the few treatments in use.
		These results further confirm the utility of PDE5 inhibitors as an oral treatment option for pulmonary hypertension and suggest that clinical trial of DA-8159 may be warranted in addition to studies in patients with erectile dysfunction which are currently underway.
	www.bioportfolio.com /LeadDiscovery/PubMed-100304.html (765 words)

	Effect of PDE5 inhibition on coronary hemodynamics in pacing-induced heart failure -- Chen et al. 284 (5): 1513 -- AJP ...
		Effect of PDE5 inhibition on coronary hemodynamics in pacing-induced heart failure -- Chen et al.
		PDE5 is found in high concentrations in the corpus cavernosum;
		The influence of PDE5 on coronary hemodynamics in the setting of congestive heart failure (CHF) has not been reported.
	ajpheart.physiology.org /cgi/content/full/284/5/H1513 (4529 words)

	Data Sheet
		Tadalafil is >10,000-fold more potent for PDE5 than for PDE1, PDE2, PDE4, and PDE7 enzymes which are found in the heart, brain, blood vessels, liver, leukocytes, skeletal muscle and other organs.
		Tadalafil is >10,000-fold more potent for PDE5 than for PDE3, an enzyme found in the heart and blood vessels.
		In a clinical pharmacology study, administration of tadalafil (10 mg) to patients with moderate renal impairment (creatinine clearance 31 to 50 mL/min) was determined to be safe but appeared to be less well tolerated in terms of back pain than in patients with mild renal impairment (creatinine clearance 51 to 80 mL/min) and healthy subjects.
	www.medsafe.govt.nz /profs/Datasheet/c/Cialistab.htm (3831 words)

	Exisulind, a Novel Proapoptotic Drug, Inhibits Rat Urinary Bladder Tumorigenesis -- Piazza et al. 61 (10): 3961 -- ...
		PDE5 was localized in discrete perinuclear foci in HT1376 cells.
		of one PDE isozyme for degrading cGMP (PDE5) and one for degrading
		PDE5 with an IC nearly identical to the GI for growth inhibition
	cancerres.aacrjournals.org /cgi/content/full/61/10/3961 (5701 words)

	Viagara Technical Information
		Viagara™, an oral therapy for erectile dysfunction, is the citrate salt of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5).
		Studies in vitro have shown that sildenafil is selective for PDE5.
		Its effect is more potent on PDE5 than on other known phosphodiesterases (>80-fold for PDE1, >1,000- fold for PDE2, PDE3, and PDE4).
	www.viagara.org.uk /technical.shtml (3977 words)

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