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PDE5 Inhibitors (pde5 + inhibitor)

Distribution by Scientific Domains

Medical Sciences	82%
Chemistry	17%

Distribution within Medical Sciences

Urology	13%
Pharmacology & Pharmaceutical Medicine	9%

Terms modified by PDE5 Inhibitors

pde5 inhibitor therapy

Selected Abstracts

ChemInform Abstract: Alternative Synthesis of Tadalafil: PDE5 Inhibitor.

CHEMINFORM, Issue 18 2009
Raghupathi Reddy Anumula
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]

SAR Development of Polycyclic Guanine Derivatives Targeted to the Discovery of a Selective PDE5 Inhibitor for Treatment of Erectile Dysfunction.

CHEMINFORM, Issue 26 2004
Dmitri A. Pissarnitski
No abstract is available for this article. [source]

Quinolines as Extremely Potent and Selective PDE5 Inhibitors as Potential Agents for Treatment of Erectile Dysfunction.

CHEMINFORM, Issue 30 2004
Yingzhi Bi
Abstract For Abstract see ChemInform Abstract in Full Text. [source]

1,7- and 2,7-Naphthyridine Derivatives as Potent and Highly Specific PDE5 Inhibitors.

CHEMINFORM, Issue 42 2003
Tatsuzo Ukita
Abstract For Abstract see ChemInform Abstract in Full Text. [source]

Success of sildenafil treatment in neurogenic female sexual dysfunction caused by L5-S1 intervertebral disk rupture: A case report

INTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2007
Dean Ferrara
Abstract: Female sexual dysfunction can be founded by disorders of sexual desire, arousal, orgasm, and sexual pain. Physiologic sexual dysfunction can, in many cases, be the result of impaired neurovascular tone to the clitoris and vagina. The vagina and clitoris both contain erectile tissue and phosphodiesterase type 5 (PDE5). Accordingly, the use of sildenafil, a PDE5 inhibitor, has been studied in relation to neurogenic female sexual dysfunction. The present case report addresses neurogenic female sexual dysfunction from the result of a ruptured L5-S1 intervertebral disk. The patient was treated with sildenafil, and her symptoms were recorded using a Female Sexual Function Index score. Discussion of the use of sildenafil in women, with an emphasis on female neurovascular sexual physiology and function, is reviewed. [source]

Synthesis of 5-ethyl-2-{5-[4-(2-hydroxyethyl)piperazin-1-ylsulfonyl]-2- n -propoxyphenyl}-7- n -propyl-3,5-dihydro-4H -pyrrolo[3,2- d]-[2- 14C]pyrimidin-4-one·2 HCl (14C-SK3530·2 HCl)

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 13 2006
Hyun-Il Shin
Abstract A new 14C-labelled PDE5 inhibitor, 5-ethyl-2-{5-[4-(2-hydroxyethyl)piperazin-1-ylsulfonyl]-2- n -propoxyphenyl}-7- n -propyl-3,5-dihydro-4H -pyrrolo[3,2- d ]-[2- 14C]pyrimidin-4-one·2 HCl (14C-SK3530·2 HCl) (1·2 HCl) was synthesized through a straightforward six-step sequence from the readily available [14C-carbonyl]methyl salicylate (2). The overall radiochemical yield of the 1·2 HCl from 2 was 10.5%, and its radiochemical purity was 98.8%. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Safety, Efficacy, and Pharmacokinetic Overview of Low-Dose Daily Administration of Tadalafil

THE JOURNAL OF SEXUAL MEDICINE, Issue 7 2009
Rebecca Wrishko PhD
ABSTRACT Introduction., Several phosphodiesterase type 5 (PDE5) inhibitors are commercially available for the treatment of erectile dysfunction (ED). Development of the first once-daily alternative dosing regimen with a PDE5 inhibitor was motivated by the behavioral complexities associated with sexual intimacy. Aim., To provide an alternative dosing option for certain men who may benefit from the removal of the temporal linkage between administration of an ED therapy and sexual intimacy or for men and their partners who anticipate at least twice-weekly sexual activity. Methods., Pharmacokinetic predictions of tadalafil plasma concentrations were generated based upon empirical data following 20-mg, single-dose administration coupled with tadalafil usage patterns from as-needed clinical trials. To support the pharmacokinetic simulations and pharmacodynamic assumptions, clinical trials were conducted to demonstrate the efficacy and safety of once-daily, low-dose tadalafil 2.5 and 5 mg. Main Outcome Measures., Simulated tadalafil plasma concentrations and comparison with safety and efficacy measures from clinical trials. Results., Based upon pharmacodynamic and pharmacokinetic data, once-daily doses of tadalafil 5 mg were predicted to provide therapeutic concentrations that would be maintained throughout the 24-hour dosing interval. Additionally, for a subgroup of men who anticipate at least twice-weekly sexual activity and are currently taking tadalafil 20 mg, a reduction in daily tadalafil exposure was predicted. To support the hypothesis that low-dose, once-daily tadalafil may be a safe and effective treatment alternative, clinical trials were conducted to demonstrate the safety and efficacy of once-daily tadalafil 2.5 and 5 mg. These results were similar to those of historical as-needed studies evaluating tadalafil 10 and 20 mg. Conclusions., Consistent with pharmacokinetic predictions, data from clinical trials indicate that once-daily use of low-dose tadalafil is a safe and effective treatment for men with ED. Wrishko R, Sorsaburu S, Wong D, Strawbridge A, and McGill J. Safety, efficacy, and pharmacokinetic overview of low-dose daily administration of tadalafil. J Sex Med 2009;6:2039,2048. [source]

The Influence of Testosterone Combined with a PDE5-inhibitor on Cognitive, Affective, and Physiological Sexual Functioning in Women Suffering from Sexual Dysfunction

THE JOURNAL OF SEXUAL MEDICINE, Issue 3 2009
Flip Van Der Made MD
ABSTRACT Introduction., Women with female sexual dysfunction have a reduced sensitivity to sexual stimuli. Activation of central mechanisms may open a window for phosphodiesterase type 5 inhibitors (PDE5) to be effective; as a consequence, the combination of testosterone and a PDE5 inhibitor will restore sexual function. Aim., To demonstrate that the combination of testosterone and vardenafil will increase the sensitivity for sexual stimuli and will improve the desire and arousal components of the sexual response. Methods., In a double-blind randomly assigned placebo-controlled crossover design, 28 women with desire and/or arousal disorder underwent four different drug treatments on four separate experimental days. A masked version of the emotional Stroop task with sexual and nonsexual words was used to measure sensitivity for sexual content. Neutral and erotic film fragments were used to determine genital,physiological and subjective reactions. Main Outcome Measures., A masked version of the emotional Stroop task, vaginal pulse amplitude. For subjective measurement, responses were collected continuously with a lever and two self-report measures were used. Results., In two subgroups, which were differentiated on the basis of their initial preconscious attentional bias for sexual cues, a different sexual response profile was found. In an initially low-attention group, preconscious attentional bias for sexual cues increased under the testosterone condition. In these women, the combination of testosterone and vardenafil caused an improvement in genital response and subjective indices of sexual functioning. In the group that had initially a high attention for sexual cues, preconscious attentional bias for sexual cues decreased under the condition of testosterone. In these women, the combination of testosterone and vardenafil had no effect on any of the indices of their sexual functioning. Conclusion., In women suffering from low sexual desire,associated with low attention for sexual cues,the combination of testosterone and vardenafil may be a promising new treatment. van der Made F, Bloemers J, Yassem WE, Kleiverda G, Everaerd W, van Ham D, Olivier B, Koppeschaar H, and Tuiten A. The influence of testosterone combined with a PDE5-inhibitor on cognitive, affective, and physiological sexual functioning in women suffering from sexual dysfunction. J Sex Med 2009;6:777,790. [source]

ORIGINAL RESEARCH,ED PHARMACOTHERAPY: Intracavernous Injections of Prostaglandin E1 for Erectile Dysfunction: Patient Satisfaction and Quality of Sex Life on Long-Term Treatment

THE JOURNAL OF SEXUAL MEDICINE, Issue 2 2007
Benjamin Alexandre MD
ABSTRACT Introduction., Since the availability of oral type 5 phosphodiesterase (PDE5) inhibitors for the treatment of erectile dysfunction (ED), patients' views on the use of intracavernous injections (ICI) of prostaglandin E1 (PGE1) may have changed. Aim., To assess the satisfaction of patients with long-term ICI. Methods., Patients with ED (>18 years old) who had used ICI of PGE1 for at least 3 months were asked to complete the "EASY" (Evaluation de l'Acceptation des injectionS dans la dYsfonction érectile) questionnaire. Main Outcome Measures., Overall patient satisfaction with ICI, impact on quality of life, ease of use, satisfaction with the quality of erections, and perceived partner satisfaction. Results., Overall, 596 questionnaires met our inclusion criteria. Mean patient age was 62.1 years, mean duration of ED was 61 months, and mean duration of ICI treatment was 35 months. Before using ICI, 43% of patients had taken at least one PDE5 inhibitor; 81% discontinued PDE5 for want of efficacy. The overall satisfaction rate with ICI was 78.3%. ICI met expectations each time in 78.6% of patients and at least half the time in 90% of patients; 86% were ready to recommend ICI to friends. Patients noted improvements in their sex life (70.1%), relationship with their partner (50%), quality of life (44.8%), and confidence in attempting sexual intercourse (80.3%). The mean number of injections was 4.4 per month. Most patients (81.1%) found the injections easy to use. The mean score for pain on injection was 2.09/10 and for pain on erection was 2.15/10. Three-quarters of patients (73.1%) thought that their partners were satisfied with ICI. Conclusion., Patients on long-term ICI/PGE1 can recover a very satisfying sex life. ICI met patients' expectations in terms of efficacy, ease of use, tolerance, and improved sex life. These results should encourage physicians and patients to use ICI when PDE5 fails, is not well tolerated, or is contraindicated. Alexandre B, Lemaire A, Desvaux P, and Amar E. Intracavernous injections of prostaglandin E1 for erectile dysfunction: Patient satisfaction and quality of sex life on long-term treatment. J Sex Med 2007;4:426,431. [source]

ORIGINAL RESEARCH,BASIC SCIENCE: Enhancement of Both EDHF and NO/cGMP Pathways Is Necessary to Reverse Erectile Dysfunction in Diabetic Rats

THE JOURNAL OF SEXUAL MEDICINE, Issue 3 2005
Javier Angulo PhD
ABSTRACT Aims and Methods., Phosphodiesterase 5 (PDE5) inhibitors are less effective in the treatment of erectile dysfunction (ED) in diabetic men than in nondiabetic patients. We have evaluated the effects of sildenafil, a PDE5 inhibitor that enhances the nitric oxide (NO)/cGMP pathway, calcium dobesilate (DOBE), which potentiates endothelium-derived hyperpolarizing factor (EDHF)-mediated responses and the combination of both on erectile responses elicited by cavernosal nerve electrical stimulation (CNES) in a rat model of ED after 8 weeks of streptozotocin-induced diabetes. Results., After 8 weeks of diabetes, erectile responses to CNES were significantly decreased in diabetic animals compared with nondiabetic time controls. While intravenous administration of sildenafil (0.3 mg/kg) or DOBE (10 mg/kg), individually, enhanced erectile responses in nondiabetic rats (214.7 ± 34.1% and 268.5 ± 30.1% of control response at 1 Hz, respectively), each failed to significantly enhance erectile responses in diabetic rats. Only when administered in combination did DOBE and sildenafil markedly potentiate erectile responses in these animals (380.1 ± 88.6% of control response at 1 Hz), completely restoring erectile function. Conclusions., These findings emphasize the importance of NO/cGMP and EDHF pathways for normal erectile function. They also give support to the in vitro observation that diabetes impairs NO and EDHF-dependent responses, precluding the complete recovery of erectile function with PDE5 inhibitors and explaining the relatively poor clinical response of diabetic men with ED to PDE5 inhibition. Finally, our study suggests that a pharmacological approach that combines enhancement of NO/cGMP and EDHF pathways could be necessary to treat ED in many diabetic men. [source]

Factors that predict changing the type of phosphodiesterase type 5 inhibitor medication among men in the UK

BJU INTERNATIONAL, Issue 4 2007
Philip D. Kell
OBJECTIVE To evaluate predictors of changing the type of phosphodiesterase type 5 (PDE5) inhibitor (switching) among men with erectile dysfunction (ED) in the UK, the largest consumer of PDE5 inhibitors in Europe, as switching medication is often associated with higher resource use, and there are three oral PDE5 inhibitor medications currently available. PATIENTS AND METHODS Patients were identified from The Health Improvement Network database in the UK; men initiating therapy with sildenafil, tadalafil or vardenafil from May 2003 to August 2004 with ,,6 months of prescription history before and after their initial PDE5 inhibitor prescription were included. Switching was evaluated as the proportion of second PDE5 inhibitor prescriptions that were for a drug differing from the first. Logistic regression was used to adjust for factors that might be associated with switching (dose, age and the presence of hypertension, dyslipidaemia, diabetes or depression). RESULTS Of the 2703 eligible men who initiated PDE5 inhibitor treatment during the study period, 91 (3.4%) switched to a different PDE5 inhibitor at their second prescription. The choice of initial PDE5 inhibitor therapy was a highly significant predictor of switching; men initiated on sildenafil were less likely to switch than those initiated on tadalafil (P < 0.001) or vardenafil (P < 0.003). Age and the presence of comorbidities were not significantly associated with switching (P > 0.05). CONCLUSION Initiating ED therapy with sildenafil was associated with the lowest rate of PDE5 inhibitor switching, which might reflect treatment satisfaction and patient preference. [source]

Animal models in urological disease and sexual dysfunction

BRITISH JOURNAL OF PHARMACOLOGY, Issue S2 2006
Gordon McMurray
There are several conditions associated with dysfunction of the lower urinary tract or which result in a reduction in the ability to engage in satisfactory sexual function and result in significant bother to sufferers, partners and/or carers. This review describes some of the animal models that may be used to discover safe and effective medicines with which to treat them. While alpha adrenoceptor antagonists and 5-alpha-reductase inhibitors deliver improvement in symptom relief in benign prostatic hyperplasia sufferers, the availability of efficacious and well-tolerated medicines to treat incontinence is less well served. Stress urinary incontinence (SUI) has no approved medical therapy in the United States and overactive bladder (OAB) therapy is limited to treatment with muscarinic antagonists (anti-muscarinics). SUI and OAB are characterised by high prevalence, a growing ageing population and a strong desire from sufferers and physicians for more effective treatment options. High patient numbers with low presentation rates characterizes sexual dysfunction in men and women. The introduction of ViagraÔ in 1998 for treating male erectile dysfunction and the success of the phosphodiesterase type 5 inhibitor class (PDE5 inhibitor) have indicated the willingness of sufferers to seek treatment when an effective alternative to injections and devices is available. The main value of preclinical models in discovering new medicines is to predict clinical outcomes. This translation can be established relatively easily in areas of medicine where there are a large number of drugs with different underlying pharmacological mechanisms in clinical usage. However, apart from, for example, the use of PDE5 inhibitors to treat male erectile dysfunction and the use of anti-muscarinics to treat OAB, this clinical information is limited. Therefore, current confidence in existing preclinical models is based on our understanding of the biochemical, physiological, pathophysiological and psychological mechanisms underlying the conditions in humans and how they are reflected in preclinical models. Confidence in both the models used and the pharmacological data generated is reinforced if different models of related aspects of the same disorder generate confirmatory data. However, these models will only be fully validated in retrospect once the pharmacological agents they have helped identify are tested in humans. British Journal of Pharmacology (2006) 147, S62,S79. doi:10.1038/sj.bjp.0706630 [source]

Role of the cardiologist: Clinical aspects of managing erectile dysfunction

CLINICAL CARDIOLOGY, Issue S1 2004
Adolph M. Hutter Jr. M.D.
Abstract Erectile dysfunction (ED) is often a marker for serious underlying cardiovascular disease (CVD), and cardiologists are increasingly involved in the care of men with ED. It is important to ask specifically about ED when evaluating men with CVD, since they may be embarrassed to volunteer this information. During the clinical workup, it is also important to check for contributing factors to ED such as diabetes, depression, stress, alcohol abuse, and cardiovascular risk factors. Patients should be advised that many treatment options are available for ED, including the phosphodiesterase type 5 (PDE5) inhibitors. The PDE5 inhibitors are safe and effective in most patients with CVD, including those taking multiple antihypertensive drugs. Furthermore, they have no deleterious effect on exercise capacity, heart rate, or extent of exercise-induced ischemia. In the future, the PDE5 inhibitors may have a role in reducing pulmonary hypertension in persons with primary pulmonary arterial hypertension (PAH) or congestive heart failure. The one major precaution for men taking PDE5 inhibitors is to avoid concomitant administration of therapeutic and recreational nitrate preparations. Patients with chest pain suggestive of a heart attack need to inform emergency room (ER) personnel if they are taking a PDE5 inhibitor. Similarly, before giving nitrates, ER personnel need to ask patients if they have used PDE5 inhibitors. Nitrates should not be given for at least 24 h after a patient uses sildenafil or vardenafil and at least 48 h after a patient uses tadalafil. [source]

Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP-binding activities

FEBS JOURNAL, Issue 9 2000
Jackie D. Corbin
In addition to its cGMP-selective catalytic site, cGMP-binding cGMP-specific phosphodiesterase (PDE5) contains two allosteric cGMP-binding sites and at least one phosphorylation site (Ser92) on each subunit [Thomas, M.K., Francis, S.H. & Corbin, J.D. (1990) J. Biol. Chem.265, 14971,14978]. In the present study, prior incubation of recombinant bovine PDE5 with a phosphorylation reaction mixture [cGMP-dependent protein kinase (PKG) or catalytic subunit of cAMP-dependent protein kinase (PKA), MgATP, cGMP, 3-isobutyl-1-methylxanthine], shown earlier to produce Ser92 phosphorylation, caused a 50,70% increase in enzyme activity and also increased the affinity of cGMP binding to the allosteric cGMP-binding sites. Both effects were associated with increases in its phosphate content up to 0.6 mol per PDE5 subunit. Omission of any one of the preincubation components caused loss of stimulation of catalytic activity. Addition of the phosphorylation reaction mixture to a crude bovine lung extract, which contains PDE5, also produced a significant increase in cGMP PDE catalytic activity. The increase in recombinant PDE5 catalytic activity brought about by phosphorylation was time-dependent and was obtained with 0.2,0.5 ,m PKG subunit, which is approximately the cellular level of this enzyme in vascular smooth muscle. Significantly greater stimulation was observed using cGMP substrate concentrations below the Km value for PDE5, although stimulation was also seen at high cGMP concentrations. Considerably higher concentration of the catalytic subunit of PKA than of PKG was required for activation. There was no detectable difference between phosphorylated and unphosphorylated PDE5 in median inhibitory concentration for the PDE5 inhibitors, sildenafil, or zaprinast 3-isobutyl-1-methylxanthine. Phosphorylation reduced the cGMP concentration required for half-maximum binding to the allosteric cGMP-binding sites from 0.13 to 0.03 ,m. The mechanism by which phosphorylation of PDE5 by PKG could be involved in physiological negative-feedback regulation of cGMP levels is discussed. [source]

Current safety and tolerability issues in men with erectile dysfunction receiving PDE5 inhibitors

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2007
W. J. G. Hellstrom
Summary Aims:, Treatment of erectile dysfunction (ED) has been greatly advanced by the advent of phosphodiesterase type-5 (PDE5) inhibitors. Upon the introduction of these agents, their cardiovascular (CV) safety was a major concern, mainly due to their vasodilatory effects. We conducted an electronic literature review of data concerning the safety and tolerability issues of men with ED receiving PDE5 inhibitors. Results:, Although safety concerns have been raised, evaluation of CV safety and related adverse events in clinical trials has not revealed any atypical safety issues. Discussion:, No causal association has been established to date between non-arteritic anterior ischaemic optic neuropathy (NAION) and PDE5 inhibitors. In addition, there are established guidelines which provide recommendations for the safe and effective use of these agents in treating men with ED and associated comorbidities. Conclusions:, Clinical trial and postmarketing surveillance data confirm the safety and tolerability profile of the PDE5 inhibitors, even in patients with endothelial dysfunction-associated comorbidities. [source]

PDE5 inhibitors in diabetic peripheral neuropathy

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2006
G. HACKETT
Summary Peripheral neuropathy is the most common complication of diabetes. This paper reviews the case histories of five patients with diabetic peripheral neuropathy or severe peripheral vascular disease who reported improvement in their symptoms when treated with regular or daily dosing with phosphodiesterase type 5 inhibitors (PDE5Is). These patients had been previously treated with PDE5Is for erectile dysfunction (ED) and not responded to on-demand therapy with a PDE5I at maximal recommended dose. This improvement is likely to be due to the known benefit of these drugs on endothelial dysfunction via an improvement of blood supply to the vasa nervorum. These cases suggest that further research is indicated to evaluate the potential use of PDE5Is in the treatment and prevention of diabetic peripheral neuropathy, particularly as these drugs are already licensed to treat ED, which occurs in around 50% of male diabetics. [source]

Prostaglandin E2 -Mediated Anabolic Effect of a Novel Inhibitor of Phosphodiesterase 4, XT-611, in the In Vitro Bone Marrow Culture,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2003
Ken-Ichi Miyamoto
Abstract The mechanism of osteoblast formation by a novel PDE4 inhibitor, XT-611, was studied in the in vitro bone marrow culture system. The compound potentiated the osteoblast differentiation through accumulation of cyclic AMP after autocrine stimulation of EP4 receptor by PGE2 in pro-osteoblastic cells. Introduction: We previously reported that inhibitors of phosphodiesterase (PDE)4 isoenzyme increase osteoblast formation in an in vitro bone marrow culture system and inhibit bone loss in animal osteoporosis models. Here we investigated the mechanism of the effect of a novel PDE4 inhibitor, 3,4-dipropyl-4,5,7,8-tetrahydro-3H -imidazo[1,2- i]-purin-5-one (XT-611), on osteoblast formation in the in vitro bone marrow culture system. Materials and Methods: Rodent bone marrow cells were cultured in the presence of 0.2 mM ascorbic acid phosphate ester, 1 mM ,-glycerophosphate, and 10 nM dexamethasone for 10 days. Drug treatments were done for 24 h on day 3 of culture. Results: PDE4 inhibitors, including XT-611, but not PDE3 and PDE5 inhibitors, increased mineralized nodule formation in rat and mouse bone marrow cell cultures. During culture of the bone marrow cells, prostaglandin E2 (PGE2) production increased with a peak on day 4, but the increase was completely inhibited by indomethacin, an unselective cyclo-oxygenase (COX) inhibitor. Spontaneous and XT-611-induced mineralized-nodule formation was also inhibited by indomethacin and COX-2 inhibitors, in a similar potential. Alkaline phosphatase-positive nodule formation in the absence or presence of XT-611 was inhibited by an antagonist of EP4 receptor, AH23848B, and synergistically potentiated by 11-deoxy-PGE1, but it was not influenced by other EP antagonists and agonists examined. The expression of PDE4 and EP4 mRNAs was observed in bone marrow cells. The effect of XT-611 was also confirmed to involve an increase of cyclic AMP and the cyclic AMP-dependent protein kinase pathway. Conclusion: These results suggest that PGE2 stimulates differentiation of osteoblast progenitor cells through the EP4 receptor in an autocrine manner, and the PDE4 inhibitor potentiates the differentiation by inhibiting hydrolysis of cyclic AMP in the cells. [source]

Angiogenesis Therapy for the Treatment of Erectile Dysfunction

THE JOURNAL OF SEXUAL MEDICINE, Issue 7 2010
Jeffrey J. Lysiak PhD
ABSTRACT Introduction., Over the past 15 years, significant advances have been made in the treatment of erectile dysfunction (ED). The most significant of these advances has been pharmacological treatment of ED with phosphodiesterase type 5 (PDE5) inhibitors. This therapy greatly increased the awareness of ED and has helped stimulate research into the underlying causes of ED. While treatment with PDE5 inhibitors continues to be the current therapy of choice, approximately 40% of men treated with PDE5 inhibitors fail to have significant improvement in erectile function and PDE5 inhibitors do not reverse the vasculopathic processes associated with ED. With this in mind, new therapies must be developed. The treatment with angiogenic growth factors such as vascular endothelial cell growth factor (VEGF) may be one such therapy. Aim., This review will focus on defining key terms in the angiogenic process, angiogenic growth factors, and different delivery methods, and summarize results from angiogenic therapies for the treatment of ED. Methods., A review of the literature was performed on all angiogenic therapies for the treatment of ED. A brief review on the angiogenic factors was also performed Results., Angiogenic therapies for the treatment of ED are possible and promising; however, further investigation is needed to advance clinically. Conclusions., Although numerous studies have now employed angiogenic factors for the possible treatment of ED in several animal models, we are still not at the point to begin human investigations. Future studies need to examine proper dosage of the angiogenic agent, route of delivery, time course for delivery, and combination therapies. Lysiak JJ, Kavoussi PK, Ellati RT, Steers WD, and Annex BH. Angiogenesis therapy for the treatment of erectile dysfunction. J Sex Med 2010;7:2554,2563. [source]

Phosphodiesterase Type 5 Inhibitors and Female Sexual Response: Faulty Protocols or Paradigms?

THE JOURNAL OF SEXUAL MEDICINE, Issue 2pt2 2010
Meredith L. Chivers PhD
ABSTRACT Introduction., Phosphodiesterase type 5 inhibitors (PDE5), such as sildenafil, tadalafil, and vardenafil, have revolutionized the treatment of erectile dysfunction. Few successes, in contrast, have been reported for the use of these agents in treatment of sexual arousal problems in women. Aim., To review research examining efficacy of PDE5 in women, critique the methods and models employed, and integrate the findings within a broader, gender-specific understanding of female sexual response. Methods., A conceptual and methodological review of all published studies examining PDE5 efficacy in female samples. Main Outcome Measures., Study methods, populations, outcome measures, study results. Results., A total of 16 studies were reviewed. Studies using self-reported measures of sexual functioning showed mixed results whereas studies examining physiological effects of PDE5 on genital vasocongestion consistently report significant effects on genital sexual response. Conclusions., The lack of efficacy of PDE5 treatment in women is likely attributable to gender differences in the concordance between physiological and psychological components of sexual response. Discordance between genital and subjective measures of sexual response in women may be augmented by PDE5 effects on genital vasocongestion in some populations, rendering successful treatment unlikely via pharmacological treatment alone. Chivers M, and Rosen RC. PDE5 inhibitors and female sexual response: Faulty protocols or paradigms? J Sex Med 2010;7:858,872. [source]

Men's Sexual Health: Evaluating the Effectiveness of Print- and PDA-based CME

THE JOURNAL OF SEXUAL MEDICINE, Issue 9 2009
Gregory A. Broderick MD
ABSTRACT Introduction., Personal digital assistant (PDA)-based continuing medical education (CME) activities have become widely available. Aims., To evaluate the effectiveness of print- and PDA-based CME materials in erectile dysfunction (ED). Methods., CME materials describing links between ED and comorbid medical conditions, effects of certain lifestyle modifications on ED, and treatment of ED with phosphodiesterase 5 (PDE5) inhibitors were distributed as a print supplement and as electronic modules, viewed with PDAs. We evaluated how effectively these materials improved evidence-based clinical choices, using survey questions about case vignettes and comparing responses of CME participants (N = 85) and matched nonparticipants (N = 94). Main Outcome Measures., Effect size, measuring the difference in evidence-based clinical scores between participants and nonparticipants. Results., CME certificates were awarded to 3,557 participants (459 print, 3,098 PDA). Among survey respondents, significantly more CME participants recognized that ED was associated with greater risk for myocardial infarction (61% participants; 34% nonparticipants; P , 0.001) and was a strong marker for diabetes mellitus (37% participants; 9% nonparticipants; P , 0.001). In contrast, participants and nonparticipants both displayed a good understanding of the relationships of smoking, obesity, and sedentary lifestyle with ED and of using PDE5 inhibitors to treat ED in patients with prostate cancer or benign prostatic hyperplasia; this likely reflects a good baseline understanding of these topics. Participants and nonparticipants each displayed a poor understanding of the recommendations regarding nonarteritic anterior ischemic optic neuropathy and PDE5 inhibitor use. Patient reluctance to discuss sexual concerns was perceived as the most significant barrier to optimal ED management. Conclusions., Given patient reluctance to discuss sexual concerns, future CME activities should focus on educating health-care providers and patients that ED is a risk factor for cardiovascular disease and diabetes. Both print- and PDA-based CME on ED were effective; the large number of lesson completers suggests a trend toward on-demand, self-selected CME is positive. Broderick GA, and Abdolrasulnia M. Men's sexual health: Evaluating the effectiveness of print- and PDA-based CME. J Sex Med 2009;6:2417,2424. [source]

ORIGINAL RESEARCH,ED PHARMACOTHERAPY: Post-Radical Prostatectomy Pharmacological Penile Rehabilitation: Practice Patterns Among the International Society for Sexual Medicine Practitioners

THE JOURNAL OF SEXUAL MEDICINE, Issue 7 2009
Patrick Teloken MD
ABSTRACT Introduction., Despite the fact that there is minimal evidence-based data supporting it, the concept of pharmacological penile rehabilitation following radical prostatectomy (RP) is receiving great attention. Aim., To define attitudes and practice patterns of clinicians who were members of the International Society for Sexual Medicine (ISSM) and/or its affiliated societies. Methods., Members of the ISSM and its regional affiliates were invited to participate in a web-based survey. Main Outcome Measures., Demographic factors, current practice status, and opinions regarding post-RP erectile dysfunction and penile rehabilitation. The statistical methods used included chi-square, Student's t -tests, and logistic regression analysis. Results., Three hundred-one physicians from 41 countries completed the questionnaire (82% were urologists). Sixty-five percent of the responders had formal sexual medicine specialty training, 44% had uro-oncology specialty training, and 60% performed RPs. Eighty-seven percent performed some form of rehabilitation. As part of the primary rehabilitation strategy, 95% used phosphodiesterase type 5 inhibitors (PDE5), 30% used vacuum device, 75% used intracavernosal injections, and 9.9% used intraurethral prostaglandin. Fifty-four percent commenced rehabilitation immediately/just after urethral catheter removal, and 37% within the first 4 months after RP. Neither the number of years in medical practice, clinician age, nor country/region of practice differed between rehabilitation performers and nonperformers. With regard to the primary reason for avoiding rehabilitation: 50% responded said it is the cost; 25% said the fact that it is not evidence-based; and 25% said they were not familiar with the concept. Performing rehabilitation was positively associated with urologic oncology training (P = 0.03), performing RP (P < 0.001), and seeing over 50 post-RP patients per year (P = 0.011). Conclusions., Among ISSM members post-RP penile rehabilitation is widely practiced, commenced early, and based predominantly on PDE5 inhibitors and intracavernosal injections. Clinicians who perform RP or see over 50 such patients per year are the most likely to perform rehabilitation. Cost represents the most common reason for rehabilitation neglect. Teloken P, Mesquita G, Montorsi F, and Mulhall J. Post-radical prostatectomy pharmacological penile rehabilitation: Practice patterns among ISSM practitioners. J Sex Med 2009;6:2032,2038. [source]

The Ontogenetic Expression Pattern of Type 5 Phosphodiesterase Correlates with Androgen Receptor Expression in Rat Corpora Cavernosa

THE JOURNAL OF SEXUAL MEDICINE, Issue 2 2009
Eleonora Carosa MD
ABSTRACT Introduction., The mechanisms controlling erection in animals and in humans are mainly age-dependent. However, the ontogenesis of the biochemical machinery of erection is largely unknown. Aim., The aim of this article was to study the expression pattern of androgen receptor (AR) and the major cyclic guanosine monophosphate-hydrolyzing enzyme present in the corpora cavernosa, type 5 phosphodiesterase (PDE5), in the rat penis during development. Methods., AR and PDE5 expression was tested on ribonucleic acids (RNAs) and proteins extracted from the whole penis or from primary cultures of smooth muscle cells obtained from the corpora cavernosa of 3- (rCC3), 20- (rCC20), and 60- (rCC60) day-old rats. Rat corpus cavernosum cells were characterized by immunocytochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Main Outcome Measures., Expression of PDE5 and AR messenger RNA (mRNA) and protein have been measured by RT-PCR and Western blot, respectively. Results., A significant increase in PDE5 mRNA expression was observed with RT-PCR from prepuberty to adulthood (0.5 ± 0.06 vs. 1.6 ± 0.046 arbitrary units [a.u.]P = 0.049). This age-dependent increase was mirrored by the increase in PDE5 protein expression found when comparing neonatal to adult corpus cavernosum smooth muscle cells (1.5 ± 0.26 vs. 4.9 ± 0.59 a.u. P = 0.0038) and the further 1.6-fold increase from rCC20 to rCC60 (4.9 ± 0.59 vs. 8.0 ± 0.8 a.u. P = 0.0024). This is the first demonstration of the ontogenetic profile of PDE5 expression in corpus cavernosum smooth muscle. As it has been demonstrated that androgens control PDE5 expression and that PDE5 inhibitors need an optimal androgenic milieu to act perfectly on erection, the expression of AR protein in rat corpus cavernosum cells was then tested by Western blot. A 7.0-fold increase was observed in primary cultured cells from 3 to 60 days old (1.4 ± 0.38 vs. 9.8 ± 1.3 a.u. P = 0.0052). Conclusion., The increase in ARs during rat penile development parallels that of PDE5 RNA and protein, thus suggesting a positive effect of androgens on PDE5 expression. Carosa E, Rossi S, Giansante N, Gravina GL, Castri A, Dolci S, Botti F, Morelli A, Di Luigi L, Pepe M, Lenzi A, and Jannini EA. The ontogenetic expression pattern of type 5 phosphodiesterase correlates with androgen receptor expression in rat corpora cavernosa. J Sex Med 2009;6:388,396. [source]

Expression of Messenger Ribonucleic Acid Encoding for Phosphodiesterase Isoenzymes in Human Female Genital Tissues

THE JOURNAL OF SEXUAL MEDICINE, Issue 6 2007
Stefan Uckert PhD
ABSTRACT Objectives., The use of inhibitors of phosphodiesterase 5 (PDE5) has been suggested to treat symptoms of female sexual dysfunction (FSD). Nonetheless, there has been a relatively low success rate of PDE5 inhibitors in FSD in comparison with male erectile dysfunction. The elevated expression of PDE5 in the human penile erectile tissue is considered the reason for the high clinical efficacy of PDE5 inhibitors in the pharmacotherapy of male erectile dysfunction. Aim., To evaluate by means of molecular biology the expression of messenger ribonucleic acid expression (mRNA) encoding for cyclic AMP and cyclic GMP PDE isoenzymes in female genital tissues. Main Outcome Measures., The amount of mRNA transcripts specifically encoding for cyclic AMP- and/or cyclic GMP-degrading PDE isoenzymes was determined. Methods., Human clitoral, labial, and vaginal tissue was obtained from four female cadavers (age at death: 18,42 years). The expression of mRNA specifically encoding for PDE1A, 1B, 1C, 2A, 4A, 5A, 10A, and 11A was elucidated by means of real-time polymerase chain reaction (PCR) analysis (TaqMan). Human penile erectile tissue (corpus cavernosum [HCC]) was used as a reference tissue. Results., mRNA encoding for all PDE isoforms mentioned above is expressed in the female genital tissues. Different magnitudes of mRNA expression were observed: a predominant expression of mRNA encoding for PDE1A but only insignificant amounts of PDE1B, 1C, 4A, 10, and 11A mRNA were registered. With PDE1A being the only exception, the mRNA expression was always higher in the HCC than in the female genital tissues. Especially, the expression of mRNA encoding for PDE5 was several-fold higher in the HCC. Conclusion., On the mRNA level, various PDE isoforms are expressed in the clitoris, labia, and vagina. It remains to be established as to whether the low expression of PDE5 in female genital tissue might be a negative predictor for the success of PDE5 inhibitors in the treatment of FSD. Uckert S, Ellinghaus P, Albrecht K, Jonas U, and Oelke M. Expression of messenger ribonucleic acid encoding for phosphodiesterase isoenzymes in human female genital tissues. J Sex Med 2007;4:1604,1609. [source]

Patients Responding to Phosphodiesterase Type 5 Inhibitor Therapy,What Do Their Sexual Partners Know?

THE JOURNAL OF SEXUAL MEDICINE, Issue 1 2007
Theodor Klotz MD
ABSTRACT Introduction., Phosphodiesterase type 5 (PDE5) inhibitors are an efficacious therapy in men with erectile dysfunction (ED). There are only a few studies that also focus on the participating couples during PDE5 inhibitor therapy. Aim., To determine to what extent patients personally informed their sexual partners about their ongoing PDE5 inhibitor therapy. Main Outcome Measures., Likelihood of informing the female partner by the patient himself about the use of PDE5 inhibitors. Methods., A total of 216 men (mean age 62.3 years) with ED were successfully treated with PDE5 inhibitors in three independent centers. After an interval of at least 3 months of successful ED therapy, all patients were asked by questionnaire whether their sexual partners were informed of their PDE5 inhibitor therapy. Results., Eighty-two percent of the patients were exclusively involved in one stable sexual relationship, 9.7% of the men admitted to having changing sexual partners, and 6% did not give any information at all about their sexual partners. Twenty percent of the men had a severe ED (International Index of Erectile Function [IIEF-5] <11). Forty-nine percent showed a moderate ED (IIEF-5 11,16) and 31% suffered a mild ED (IIEF-5 >16). PDE5 inhibitor medication was used 1.2 times/month by men with a severe ED, 2.1 times/month by patients with a moderate ED, and 2.9 times/month by men with a mild ED. Forty-one (93%) of the 44 patients with a severe ED informed their sexual partners that they were taking PDE5 inhibitors. In the patient group with moderate ED, 49 (47%) of 105 patients and only 14 (21%) of 67 of the patients with mild ED shared this information with their partners. Conclusion., Less than 40% of the patients suffering a moderate or mild ED using PDE5 inhibitors shared this information with their partners. It seems that patients find ED so disturbing that many patients do not inform their partners of PDE5 inhibitor use. Klotz T, Mathers M, Klotz R, and Sommer F. Patients responding to phosphodiesterase type 5 inhibitor therapy,What do their sexual partners know? J Sex Med 2007;4:162,165. [source]

Feasibility of the Use of Phosphodiesterase Type 5 Inhibitors in a Pharmacologic Prevention Program for Recurrent Priapism

THE JOURNAL OF SEXUAL MEDICINE, Issue 6 2006
Arthur L. Burnett MD
ABSTRACT Introduction., Recurrent ischemic priapism is an enigmatic erectile disorder in need of improved clinical interventions to avert its known, potentially serious complications. Aim., To evaluate the use of a long-term, continuous phosphodiesterase type 5 (PDE5) inhibitor therapeutic regimen in controlling recurrent ischemic priapism and its feasibility in a clinical management program for the disorder. Main Outcome Measures., The main outcome measure was reduction in frequency or duration of priapism episodes. A secondary outcome measure was preservation of erectile ability. Methods., We retrospectively evaluated the clinical progress of seven patients (age 22,37 years) with sickle cell disease-associated "stuttering" priapism (N = 4) and idiopathic recurrent priapism (N = 3), who were counseled and consented to the "off-label" use of the PDE5 inhibitors sildenafil citrate and tadalafil. The medications were administered according to a specified therapeutic regimen based on scientific evidence that chronic PDE5 inhibitor administration in priapism contexts effectively reconditions PDE5 regulatory function in the penis. The duration of clinical follow-up extended through 2 years. Results., All seven patients were confirmed to have recurrent ischemic priapism without identifiable pharmacologic, traumatic, or neoplastic disease associations based on clinical history, physical examination, laboratory testing, and penile diagnostics. PDE5 inhibitor treatment was successful in alleviating or resolving priapism recurrences in six of the seven patients. Erectile function was unchanged in six patients and improved in one patient at last follow-up compared with baseline status. All the patients reported that PDE5 inhibitor therapy was well tolerated and did not cause any adverse effects limiting their continued use of the medication. Conclusions., Because of their efficacy, safety, and tolerability as shown in this case series, PDE5 inhibitors would appear to have a possible role in a rigorously implemented clinical management program to control recurrent priapism. However, completion of a controlled clinical trial is necessary to confirm the utility of this treatment. Burnett AL, Bivalacqua TJ, Champion HC, and Musicki B. Feasibility of the use of phosphodiesterase type 5 inhibitors in a pharmacologic prevention program for recurrent priapism. J Sex Med 2006;3:1077,1084. [source]

ORIGINAL RESEARCH,BASIC SCIENCE: Enhancement of Both EDHF and NO/cGMP Pathways Is Necessary to Reverse Erectile Dysfunction in Diabetic Rats

ORIGINAL RESEARCH,BASIC SCIENCE: A Nitric Oxide-Releasing PDE5 Inhibitor Relaxes Human Corpus Cavernosum in the Absence of Endogenous Nitric Oxide

THE JOURNAL OF SEXUAL MEDICINE, Issue 1 2005
Jasjit S. Kalsi BSc, MRCS
ABSTRACT Introduction., In conditions with severe deficiency of endogenous nitric oxide (NO), such as long-term diabetes and cavernosal nerve injury, phosphodiesterase type 5 (PDE5) inhibitors have reduced efficacy in the treatment of erectile dysfunction. NO-releasing PDE5 inhibitors could be an alternative therapeutic approach in such cases. Aim., We therefore aimed to compare sildenafil and NO-releasing sildenafil (NCX-911) in relaxing human corpus cavernosum in the absence or presence of endogenous NO. Methods., The two compounds were compared in reducing the phenylephrine-induced tone of human corpus cavernosum in the presence or absence of an inhibitor of NO synthase (L-NAME; 500 µM) or an inhibitor of soluble guanylate cyclase (ODQ, 10 µM). Results., NCX-911 was as potent as sildenafil in control conditions (EC50 = 733.1 ± 94.4 nM and 800.7 ± 155.8 nM, respectively). The potency of NCX-911 was not altered but that of sildenafil decreased significantly in the presence of L-NAME (EC50 = 980.4 ± 106.7 nM and 2446.7 ± 256.8 nM, respectively; P < 0.001 for sildenafil vs. control). Both compounds below 1 µM failed to induce relaxation in the presence of ODQ (EC50 = 6578 ± 1150 nM and 6488 ± 938 nM for NCX-911 and sildenafil, respectively). Conclusion., These results show that the potency of NCX-911 was maintained unlike sildenafil in the absence of endogenous NO confirming the potential use of NO-releasing PDE5 inhibitors in NO-deficient conditions. [source]

Tadalafil and vardenafil vs sildenafil: a review of patient-preference studies

BJU INTERNATIONAL, Issue 9 2009
Vincenzo Mirone
The immediate objective of phosphodiesterase type 5 (PDE5) inhibitor treatment is to restore the ability of a man to achieve and/or maintain an erection adequate for sexual intercourse. As erectile dysfunction (ED) generally develops in the second half of life, the ultimate objective generally is not procreation, but quality of sexual life. Indeed, ED is known to impair quality of life considerably; two-thirds of men report that ED has impaired their self-esteem and nearly a third claim that it has damaged the relationship with their partner. It follows that the therapeutic success of PDE5 inhibition has an important subjective component, which is compounded by the subjective nature and complexity of sexual life in humans. This makes it very difficult for physicians to be certain that they have selected the optimal therapy for a couple, even after a thorough evaluation. The 2007 European Association of Urology Guidelines stress the importance of educating the patient and claim that ,the patient will choose the final drug after his own experience'. However, PDE5 inhibitors are typically used twice a week, so a patient would have to spend ,3 months trying the various compounds and dosages to achieve adequate exposure to all three PDE5 inhibitors; this would seem an unrealistic strategy in normal clinical practice. The acknowledgement that the patient has an important role in therapeutic decisions for ED has fuelled interest in the concept of patient preference. It has been established that patient preference depends on three factors, i.e. personal characteristics, e.g. age, duration of ED, frequency and dynamics of sexual relations, and the characteristics of their partners, e.g. age, menopausal status and level of interest in sexual activity and medication profile. Medication features of interest include efficacy in terms of quality of erection, consistency of effects, rapid onset of action, long duration of action, side-effect profile and route of administration; drug costs must also be considered if the medicinal product is not reimbursed. [source]