vardenafil, Levitra
Comparison of clinical trials with sildenafil, vardenafil and tadalafil in erectile dysfunction.

Doggrell SA.

Doggrell Biomedical Communications, 47 Caronia Crescent, Lynfield, Auckland, New Zealand. s_doggrell yahoo.com.

Erectile dysfunction (ED) affects up to 50% of men, between 40 and 70years of age. In the first major trial of sildenafil in ED, at 24weeks, improved erections were reported by 77 and 84% of men taking sildenafil 50 and 100mg, respectively. Subsequently, sildenafil has been reported to be effective in men with ED associated with diabetes and prostate cancer, and in psychogenic ED. Sildenafil is safe in men with coronary artery disease, provided it is not used with the nitrates (a contraindication). The most commonly reported adverse effects with sildenafil are headache, flushing and dyspepsia. Vardena-fil is more potent and more selective than sildenafil at inhibiting phosphodiesterase-5. Vardenafil is similarly effective to sildenafil in the treatment of ED. The only advantage that vardenafil has over sildenafil is that it does not inhibit phosphodiesterase-6 to alter colour perception, a rare side effect which sometimes occurs with sildenafil. Tadalafil has a longer duration of action than sildenafil and vardenafil. Tadalafil is similarly effective as sildena-fil in the treatment of ED. In comparison studies, tadalafil is preferred to sildenafil (50/100mg) by men with ED, possibly because of its longer duration of action. Of the phosphodiesterase inhibitors, tadalafil may displace sild-enafil as the drug of choice among men with ED.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15709885&dopt=Abstract vardenafil Levitra



vardenafil, Levitra
Recreational use and misuse of phosphodiesterase 5 inhibitors.

Smith KM, Romanelli F.

Drug Information Center, College of Pharmacy, University of Kentucky, Lexington, 40536-0293, USA. ksmit1 email.uky.edu

OBJECTIVE: To characterize the rationale for and extent of phosphodiesterase (PDE) 5 inhibitor use in recreational settings, describe risks from such misuse, and discuss postexposure clinical management strategies. DATA SOURCES: Published articles identified by searches through Medline, EMBASE, International Pharmaceutical Abstracts, and Toxline, from 1990 to March 2004, using the search terms sildenafil, tadalafil, vardenafil, phosphodiesterase inhibitor, abuse, overdose, adverse effects, recreational, and street drugs. Additional references identified within articles and information from the Internet were included. STUDY SELECTION: Clinical trials, epidemiologic reviews, case reports, and news releases concerning the misuse of sildenafil. DATA EXTRACTION: By the authors. DATA SYNTHESIS: PDE5 inhibitors, indicated for treatment of erectile dysfunction, can produce several adverse effects, including potentially fatal cardiovascular events. Reports of recreational use and misuse of sildenafil appear in the medical literature and the media. The potential for abuse also exists for the two more recently approved drugs in this class, vardenafil and tadalafil. Increasing access to these drugs via the Internet may facilitate such misuse. Use in social settings has gained popularity, both in young, healthy patients, as well as those with chronic medical conditions, including human immunodeficiency virus infections. In these settings, the PDE5 inhibitors are sometimes used concomitantly with "club drugs" such as ketamine and amyl nitrite, leading to potentially harmful or fatal drug interactions. CONCLUSION: Pharmacists should be cognizant of the potential for PDE5 inhibitors to be misused, particularly in patients who are at greater risk of cardiovascular complications, and should advise patients and other health care professionals accordingly.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15730119&dopt=Abstract vardenafil Levitra



vardenafil, Levitra
Efficacy of vardenafil and sildenafil in facilitating penile erection in an animal model.

Choi S, O'Connell L, Min K, Kim NN, Munarriz R, Goldstein I, Bischoff E, Traish AM.

Department of Urology, Boston University School of Medicine, Massachusetts 02118, USA.

Vardenafil and sildenafil are potent and specific phosphodiesterase type 5 (PDE 5) inhibitors. In human penile cavernosal smooth muscle cells, we have previously shown that vardenafil has a lower biochemical inhibition constant (Ki) than sildenafil. In this study, we compared the efficacy of vardenafil and sildenafil in facilitating penile erection in a rabbit model. Penile erections were elicited by submaximal (2.5 or 6 Hz) pelvic nerve stimulation (PNS) repeated every 5 minutes for 30 minutes with or without intravenous (i.v.) administration of vardenafil (1-30 microg/kg) or sildenafil (10-30 microg/kg). Erectile response was assessed by continuously recording intracavernosal pressure (ICP) and systemic arterial pressure (SAP). All data were expressed as a ratio of ICP:SAP. I.v. administration of either PDE 5 inhibitor facilitated PNS-induced erection and increased ICP:SAP in a dose-dependent manner, reaching peak response at approximately 5 minutes. However, the threshold dose at which facilitation of erection occurred was lower for vardenafil (3 microg/kg) than for sildenafil (10 microg/kg). At the 10-microg/kg dose (i.v.), the response duration was significantly greater with vardenafil (169 +/- 23 seconds) than with sildenafil (137 +/- 31 seconds). Direct intracavernosal (i.c.) injection of 1-30 microg/kg vardenafil or sildenafil also caused dose-dependent increases in ICP:SAP in the absence of PNS. Response durations increased in a dose-dependent manner and lasted more than 5 times that of i.v. drug administration coupled with PNS. Irrespective of the route of administration (i.c. or i.v.), at equivalent doses, vardenafil was significantly more efficacious than sildenafil in facilitating pelvic nerve-mediated penile erection and in eliciting erection in the absence of PNS. The increases in ICPs occurred more quickly, were of larger magnitude, and were sustained for longer durations for vardenafil than for sildenafil. On the basis of the biochemical data and physiological responses from this study, further clinical evaluation of vardenafil as treatment for erectile dysfunction is warranted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12002434&dopt=Abstract vardenafil Levitra



vardenafil, Levitra
Effects of two selective phosphodiesterase type 5 inhibitors, sildenafil and vardenafil, on object recognition memory and hippocampal cyclic GMP levels in the rat.

Prickaerts J, van Staveren WC, Sik A, Markerink-van Ittersum M, Niewohner U, van der Staay FJ, Blokland A, de Vente J.

Department of Psychiatry and Neuropsychology, European Graduate School of Neuroscience EURON, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. jos.prickaerts np.unimaas.nl

The present study investigated the effects of two cyclic GMP-specific phosphodiesterase enzyme type 5 inhibitors, sildenafil and vardenafil, on the memory performance in the object recognition task. Both compounds were given per orally (1, 3 and 10 mg/kg sildenafil; 0.1, 0.3, 1 and 3 mg/kg vardenafil) immediately after the exposure to two identical objects. The memory for the objects was tested 24 h later. Vehicle-treated rats spent equal times exploring a new and the familiar object demonstrating that they did not remember the familiar one. However, sildenafil improved the object discrimination performance of the rats with a high discrimination performance at a dose of 3 mg/kg. Rats treated with vardenafil also showed an improved object discrimination performance. Compared with sildenafil, vardenafil appeared to be even more potent in this respect since it already produced a high discrimination performance at a dose of 0.3 mg/kg. The effects of both compounds on cyclic GMP and cyclic AMP accumulation were studied in rat hippocampal slices incubated in vitro. Cyclic GMP levels were increased after incubation with the highest concentration of 100 microM vardenafil (together with 0.1 mM sodium nitroprusside), although no changes in cyclic GMP levels were detected after incubation with different concentrations of sildenafil. Both compounds had no effect on cyclic AMP levels. Additional cyclic GMP immunocytochemistry showed that incubation with vardenafil (in the presence of sodium nitroprusside) resulted in a concentration-dependent staining of cyclic GMP. Staining was predominantly found in neuronal fibres in the hippocampal CA2/CA3 region. It was already detected at a concentration of 0.1 microM vardenafil. Also positive fibres were detected after incubation with sildenafil but at a higher concentration of 10 microM. Taken together, these results suggest that inhibition of phosphodiesterase enzyme type 5 improves object recognition memory. This effect might be explained by increased levels of central cyclic GMP. Copyright 2002 IBRO

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12127092&dopt=Abstract vardenafil Levitra