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PubMed2002

Efficacy and safety of sildenafil for treating erectile dysfunction in patients on dialysis.

OBJECTIVE: To assess the efficacy of sildenafil for erectile dysfunction (ED) in patients on haemodialysis (HD) or peritoneal dialysis (PD), as men with end-stage renal disease (ESRD) often have sexual dysfunction (up to 82% among those on chronic dialysis). PATIENTS AND METHODS: Forty-one patients with ED and in ESRD participated in an open-label prospective study. Thirty patients on HD and 11 on PD were asked to complete the International Index of Erectile Function (IIEF) and Fugl-Meyer life-satisfaction scale before and after sildenafil treatment. A total score in the erectile function domain of < or = 25 was accepted as indicating ED. All patients were started on a 25-mg dose, which was increased to 50 mg if there was no response after two trials. In addition, the overall efficacy question was used to evaluate satisfaction, and patients reported any side-effects during treatment. RESULTS: The erectile function and intercourse satisfaction domains improved significantly in both groups (P < 0.01). After sildenafil treatment, two-thirds of those on HD (20/30) and nine of the 11 on PD recovered their erectile function. The pretreatment scores on the IIEF and four domains (except sexual desire) of those responding were significantly higher than in those not responding (P < 0.05). The satisfaction rate on the overall efficacy question was 80% and 82% for the HD and PD groups, respectively. At least one side-effect was seen in 17 patients (43%); one had severe hypotension in the PD group. Overall, mild headache (seven patients, 18%) and flushing (12, 30%) were reported most often. CONCLUSIONS: Sildenafil is a safe and satisfactory drug for improving erectile function in patients with ESRD. Patients were satisfied whether treated by HD or PD. Pretreatment scores on the IIEF may be useful for predicting the success of treatment.

Adult↗
PubMed2000

Erectile dysfunction in men with obstructive sleep apnea: an early sign of nerve involvement.

Erectile dysfunction (ED) is common in men with obstructive sleep apnea (OSAS) but no completely convincing hypotheses about the underlying pathogenic mechanisms have been published in the literature. The aims of the present study were to assess the presence of ED in a group of OSAS patients without daytime respiratory failure and to determine whether this dysfunction was related to peripheral nerve involvement. Evaluation of the bulbocavernosus reflex (BCR) and the somato-sensory evoked potentials of pudendal nerve (PSEPs), the most widely established method of documenting pudendal neuropathies as being the cause of impotence, was performed in 25 patients. Data on BCR were compared with those of 25 healthy males volunteers matched for age. BCR was altered in 17 patients: in 6 it was elicited while in 11 it had a prolonged latency and reduced amplitude. Patients with altered BCR presented an higher AHI, an higher percentage of sleep time spent with SaO2 <90% (TST90) and a lower daytime PaO2. Six patient had clinically silent neurophysiological signs of mild polyneuropathy. The degree of OSAS and gas exchange alteration was more severe in patients with polyneuropathy than in those with isolated BCR alteration. ED is a common finding in OSAS patients and this alteration seems to be related to a nerve dysfunction. The development of nerve dysfunction is associated with a more severe degree of OSAS and nocturnal hypoxia.

Arousal↗
PubMed2004

Association of lower urinary tract symptoms with erectile dysfunction in Japanese men.

OBJECTIVES: To assess the age-stratified prevalence of erectile dysfunction (ED) and how lower urinary tract symptoms (LUTS) are associated with ED, and to estimate the correlates of ED among Japanese men. METHODS: A self-administered questionnaire of the International Prostate Symptom Score and the abridged 5-item version of the International Index of Erectile Function were given to 3189 noninstitutionalized men during a multiphasic health screening. The data from 2084 men who provided complete responses to the questionnaire were analyzed. RESULTS: The prevalence of moderate to severe ED increased from 13.4% among those younger than 40 years to 20.6%, 39.9%, and 63.1% among those aged 40 to 49, 50 to 59, and 60 years or older, respectively. Most were dissatisfied with their sex life regardless of age. The severity of ED was significantly associated with moderate to severe International Prostate Symptom Scores (age-adjusted odds ratio 1.52), specifically in the urgency (1.75) and nocturia (1.36) domains, and for those with diabetes mellitus (2.54) and coronary artery disease (8.04). CONCLUSIONS: ED is highly prevalent among Japanese men with LUTS and is significantly associated with the severity of LUTS after controlling for age. This significant aspect of life for men of all ages should be taken into account when treating patients with LUTS.

Adult↗
PubMed2003

A multicenter, randomized, double-blind, crossover study of patient preference for tadalafil 20 mg or sildenafil citrate 50 mg during initiation of treatment for erectile dysfunction.

BACKGROUND: Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor approved in >30 countries for the treatment of erectile dysfunction (ED). It has been shown to improve erectile function compared with placebo in Phase III studies, but clinical experience comparing tadalafil with the PDE5 inhibitor sildenafil citrate is lacking. OBJECTIVE: This study compared patient preference for tadalafil 20 mg or sildenafil 50 mg during initial treatment for ED. It also compared the tolerability of the 2 agents at these doses. METHODS: This randomized, double-blind, fixed-dose, 2-period crossover trial took place at 13 sites in the United States and Germany. Patients were randomized 1:1 to receive 4 weeks of treatment with tadalafil 20 mg or sildenafil 50 mg, followed by the alternative treatment, to be taken as needed up to once daily before sexual activity. RESULTS: The study enrolled 215 men with ED, 109 randomized to the tadalafil-sildenafil sequence and 106 to the sildenafil-tadalafil sequence. Their mean age was 49.8 years; 84.7% were sildenafil naive and 15.3% had undergone a previous inadequate trial of sildenafil. Most patients had moderate ED (60.5%) of >or=1 year's duration (74.9%). Of 190 evaluable patients, 126 (66.3%) preferred to initiate treatment with tadalafil, compared with 64 (33.7%) with sildenafil (P < 0.001). Patients' preference did not differ by age, duration of ED, treatment sequence, or previous sildenafil exposure. Both medications were well tolerated, with no significant differences in the incidence of treatment-emergent adverse events. Headache (11.2% tadalafil, 8.8% sildenafil), dyspepsia (6.0% and 4.2%, respectively), nasopharyngitis (4.7% and 2.8%), and flushing (2.8% and 4.7%) were the most common adverse events. The rate of ocular disturbances was low: 1 patient experienced intermittent bilateral reduction in visual acuity with tadalafil, and 2 exhibited conjunctival hyperemia or eyelid edema with sildenafil. CONCLUSIONS: Tadalafil 20 mg was preferred to sildenafil 50 mg for the initiation of ED therapy in this study population. Both medications were well tolerated.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2004

Severe, but not mild, obstructive sleep apnea syndrome is associated with erectile dysfunction.

OBJECTIVES: To assess the association between obstructive sleep apnea syndrome (OSAS) and erectile dysfunction (ED). OSAS is associated with fatigue and daily dysfunction. We hypothesized that OSA severity will correlate with ED. We also sought to determine the specific features with predictive value for ED in patients with OSAS. METHODS: A total of 209 patients evaluated for potential OSAS were given a sleep questionnaire, a revised International Index of Erectile Function questionnaire (composed of three main topics: sexual satisfaction, erection during intercourse, and morning erection), and then underwent a full-night in-laboratory polysomnography examination. The data were scored blindly. RESULTS: A decrease in erectile function was found in all OSAS groups compared with those without OSAS. However, the only group for whom this reduction was statistically significant (P <0.05) in all ED dimensions was the severe OSAS group (respiratory disturbance index [RDI] greater than 40). Furthermore, the patients complaining of severe ED had the greatest RDI. Stepwise multiple logistic regression analyses revealed that the predicting factors for ED in OSAS patients were age, morning tiredness, and RDI. CONCLUSIONS: Severe OSAS is clearly associated with ED. However, the relationship is very weak in patients with mild or moderate OSAS. The predictive factors for ED in patients with OSAS include age, morning tiredness, and RDI.

Adult↗
PubMed2002

Low-flow priapism: risk factors for erectile dysfunction.

OBJECTIVE: To evaluate our policy of managing priapism for the success rate of the treatments, potency afterward, complications, and the risk factors responsible for erectile dysfunction in these patients. PATIENTS AND METHODS: The study included 50 patients (mean age 37.1 years, range 22-66) with a diagnosis of priapism (1981-1999). Their records were reviewed; 35 patients were available for a long-term evaluation. Factors assessed were the duration of priapism, history of previous recurrent attacks, possible underlying causes (e.g. haematological disorders, medications or trauma), relation to sexual stimulation, pain, and any attempt at previous management. A complete blood screen and blood gases were assessed in corporal aspirates. Duplex ultrasonography was used in all impotent patients at their follow-up. Early and late complications were reviewed, and patients asked about their erectile function before priapism, and any recurrence. RESULTS: The median (range) duration of priapism was 48 (6-240) h; almost half the patients presented > 48 h after the onset of priapism. Sixteen patients (32%) reported a history of previous recurrent attacks, of whom seven had a history of previous treatments. The main cause of priapism was idiopathic or intracavernosal injection with papaverine. All patients were initially treated by corporal blood aspiration and injection with ephedrine; if this failed or if the priapism was prolonged (> 48 h) various shunts were used. The hospital stay was significantly shorter among patients with papaverine-induced or brief priapism. In the long-term follow-up of 35 patients (mean 66.4 months, range 3-220) only 15 (43%) reported preserved erectile function, and this was more likely in patients with brief priapism (< 48 h). Eight patients (23%) reported subsequent recurrent attacks of priapism; all were managed successfully as they presented shortly after their onset. Penile fibrosis was detected in 20 patients (57%), and was significantly more common in those with prolonged priapism (> 48 h) or from causes other than papaverine. The 20 impotent men evaluated by Doppler ultrasonography had severe echo-dense penile fibrosis and high end-diastolic velocities suggesting veno-occlusive incompetence in all except two. In five men with shunts cavernosography showed extensive venous leakage irrespective of site of the shunt. MRI in five patients with penile fibrosis showed heterogeneous areas of low signal intensity, corresponding with haemosiderin deposition and fibrosis. On univariate analysis the final result of management (complete detumescence or not), the duration of priapism and the presence of penile fibrosis significantly influenced erectile function. On multivariate logistic regression only the first remained significant. CONCLUSIONS: Low-flow priapism for > 48 h, failure to maintain complete detumescence after management, and marked penile fibrosis during the follow-up are the most significant risk factors responsible for erectile dysfunction, with failure to achieve complete detumescence the most detrimental.

Adult↗
PubMed2005

Advances in the Management of Post-Radical Prostatectomy Erectile Dysfunction: Treatment Strategies When PDE-5 Inhibitors Don't Work.

Phosphodiesterase type-5 (PDE-5) inhibitors have revolutionized the treatment of post-radical prostatectomy erectile dysfunction. For those patients who undergo a non-nerve-sparing radical prostatectomy or whose condition fails to respond to PDE-5 inhibitors, alternative treatment with intracavernous injection therapy, transurethral alprostadil, vacuum erection devices, and recently described combination therapy is available. The goals of therapy are to provide the patient with a means of obtaining an erection so that the patient and his partner may resume sexual relations as soon as possible following radical prostatectomy. There is evidence that early institution of treatment may promote improvement in the return of spontaneous erections in patients who have undergone nerve preservation. In patients who undergo non-nerve-sparing procedures, therapy may improve penile rigidity. Intracavernous injection therapy, transurethral alprostadil, and vacuum devices are highly effective in the management of post-prostatectomy erectile dysfunction. High dropout rates, which are not related to adverse effects, have been described with all 3 modalities. Pre- and postoperative counseling may improve patient and partner satisfaction.

Journal Article↗
PubMed2006

Soluble guanylate cyclase beta1-subunit expression is increased in mononuclear cells from patients with erectile dysfunction.

The aim was to determine in circulating mononuclear cells from patients with erectile dysfunction (ED), the level of expression of endothelial nitric oxide synthase (eNOS), soluble guanylate cyclase (sGC) beta1-subunit and phosphodiesterase type-V (PDE-V). Peripheral mononuclear cells from nine patients with ED of vascular origin and nine patients with ED of neurological origin were obtained. Fourteen age-matched volunteers with normal erectile function were used as control. Reduction in eNOS protein was observed in the mononuclear cells from patients with ED of vascular origin but not in those from neurological origin. Although sGC beta1-subunit expression was increased in mononuclear cells from patients with ED, the sGC activity was reduced. However, only the patients with ED of vascular origin showed an increased expression of PDE-V. This work shows for the first time that, independently of the aetiology of ED, the expression of sGC beta1-subunit was increased in circulating mononuclear cells; however, the expression of both eNOS and PDE-V was only modified in the circulating mononuclear cells from patients with ED of vascular origin.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Efficacy of shunt surgery for refractory low flow priapism: a report on the incidence of failed detumescence and erectile dysfunction.

PURPOSE: The reported success rate for surgical cavernosa-to-spongiosum shunts in patients with refractory low flow priapism is variable and yet it is reported to be as high as 100% in terms of achieving detumescence. The long-term potency rate after the introduction of the shunt procedure is also as high as 50%. We reviewed the efficacy of various shunts in terms of achieving detumescence and we clarified the rate of erectile dysfunction at long-term followup. MATERIALS AND METHODS: Patients were included in the analysis if they had painful low flow priapism more than 4 hours in duration that was refractory to conservative management, ultimately requiring a surgical shunt. Data, including etiology, duration and initial treatment measures, were retrospectively compiled in the last 12 years and the type of surgical shunts performed were recorded. Followup erectile function was assessed by clinical notes and a telephone survey using the International Index of Erectile Function. RESULTS: Of the 28 consecutive patients included in the study 13 (46.4%) required more than 1 operation for failed detumesence, of whom 12 (92.3%) initially underwent a Winter shunt. Only 2 of the 20 men (10%) with available followup reported preservation of pre-morbid erectile function. Three men (15%) achieved partial erection without the assistance of oral or injectable agents. CONCLUSIONS: In contrast to previously reported success rates, approximately 50% of our patients required reoperation for failed detumescence following a cavernosa-to-spongiosum shunt. In our experience the Winter shunt was the least successful operation, whereas reoperation was uncommonly required following an Al-Ghorab or Quackels shunt. As many as 90% of our patients had erectile dysfunction at followup.

Adolescent↗
PubMed2001

The history of erectile dysfunction management.

This article describes the evolution or revolution in the management of erectile dysfunction over the centuries. In recent history there has been a rapid movement away from a predominant role for the specialist towards the primary care physician. The physician is increasingly faced with the need to individualize therapy to meet patient expectations.

Erectile Dysfunction↗
PubMed2006

Elevated RhoA/Rho-kinase activity in the aged rat penis: mechanism for age-associated erectile dysfunction.

Epidemiologic studies have shown that aging accounts significantly for the prevalence of erectile dysfunction (ED). The pathophysiology of ED during aging and its underlying molecular mechanisms are largely unknown. We hypothesized that increased RhoA/Rho-kinase signaling is a major factor in the pathogenesis of age-associated ED and the mechanism involves increased penile smooth muscle contractility through inhibition of myosin light chain phosphatase. Male Fischer 344 young (4 month old) and aged (20-22 month old) rats underwent erectile function testing in vivo by measuring intracavernosal pressure (ICP) and mean arterial blood pressure (MAP) upon electrical stimulation of the cavernous nerve. The data demonstrated that erectile function was significantly lower in aged rats than that in young rats at all voltages tested (P<0.05). Western blot analysis results showed that there were no significant changes in protein expressions of RhoA, Rho-kinase-alpha and -beta isoforms, and myosin light chain phosphatase target subunit (MYPT1); however, membrane-bound RhoA and phosphorylated MYPT1 were increased in aged rat penes by 95 +/- 15 and 56 +/- 8% (P<0.05), respectively, indicating enhanced RhoA and Rho-kinase activity. Inhibition of Rho-kinase with Y27632 maximally increased ICP/MAP to 0.72 +/- 0.05 in aged rats vs. 0.47 +/- 0.06 in young rats (P<0.05). Gene transfer of adeno-associated virus (AAV) encoding dominant negative RhoA (T19NRhoA) to penes of aged and young rats for 7 days markedly improved erectile function in aged rats when compared with that in young rats (P<0.05). These observations were also supported by Rho-kinase activity assay results showing that basal Rho-kinase activity in aged rat penes receiving AAV vehicle treatment was twofold greater than that in young rat penes receiving AAV vehicle treatment, while it was reduced to a level similar to that in young rat penes after gene therapy of T19NRhoA (P<0.05). Taken together, these data suggest that impaired erectile function during the aging process involves increased RhoA/Rho-kinase signaling, and this pathway may be exploited for the treatment of age-associated ED.

Aging↗
PubMed2005

Arteriogenic erectile dysfunction alters protein expression within the cavernosal tissue in an animal model.

INTRODUCTION: Erectile dysfunction (ED) is a highly prevalent and often untreated condition. It may be a marker of underlying chronic illness and negatively impacts quality of life. Penile arterial insufficiency, frequently found in association with hypertension, dyslipidemia, diabetes mellitus, pelvic irradiation, trauma, and smoking, is the most common cause of ED. AIM: This study was designed to measure the effect of penile hypoperfusion-induced alteration and injury on erectile tissue at the cellular and protein level. METHODS: Eighteen 4-month-old male Sprague Dawley rats were placed into three groups (n = 6): sham surgery, unilateral internal iliac artery ligation (UIIAL), and bilateral internal iliac artery ligation (BIIAL). MAIN OUTCOME MEASURE: Erectile function was assessed 4 weeks following arterial ligation surgery as measured by a rise in intracavernosal pressure induced by cavernosal nerve stimulation. Penile tissue alterations were characterized by immunohistochemistry, protein content measured by western blot, and "global" protein expression profile carried out by using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip technology. RESULTS: Significantly lower intracavernous pressures were demonstrated in animals subjected to UIIAL surgery, which correlated to the extent of artery ligation. The intensity and quantity of immunohistochemical staining for neuronal nitric oxide synthase, endothelial cell integrity, smooth muscle cell alpha-actin, and vascular endothelial growth factor (VEGF) receptor flk1 were decreased in the BIIAL group compared to sham controls. SELDI-TOF-MS analysis revealed changes in molecular expression of a approximately 6,560 Da protein relative to a 7,720 Da protein (peak ratio = 1.34 +/- 0.3, BIIAL; 0.36 +/- 0.1 controls, P < 0.05). CONCLUSIONS: In this report, an animal model of vascular penile insufficiency demonstrates altered protein expression associated with cavernosal tissue injury and reduced erectile function. Although the clinical significance of these observations is currently undefined, this model may allow greater insight into the complex biologic changes associated with arteriogenic ED in man.

Actins↗
PubMed2001

Evaluation of oral ro70-0004/003, an alpha1A-adrenoceptor antagonist, in the treatment of male erectile dysfunction.

Alpha-adrenoceptor antagonists have been used for the treatment of male erectile dysfunction (MED). Ro70-0004/003 (Ro70-0004) is a selective and orally active alpha1A-adrenoceptor antagonist. The objective of this study was to: (1) pharmacologically elucidate the alpha1-adrenoceptor subtype mediating norepinephrine-induced contraction of human isolated corpus cavernosal tissue and (2) conduct a clinical proof-of-concept study with Ro70-0004 to test the hypothesis that selective alpha1A-adrenoceptor blockade would improve erectile function in patients with MED. In vitro organ bath studies were conducted with strips of human isolated corpus cavernosal tissue obtained from patients undergoing penile prosthesis implantation. Prazosin, cyclazosin, RS-100329 and Ro70-0004/003 antagonized norepinephrine-induced contractile responses with affinity estimates (pK(B) or pA2) of 8.4, 7.3, 9.2 and 8.8, respectively, consistent with the singular involvement of alpha1A-adrenoceptor subtype. A clinical study (single center, observer-blind, randomized, placebo-controlled, extended period Latin-Square crossover design) was conducted in 24 male patients (mean age 44 y) with MED of no established organic cause to evaluate the efficacy of a 5-mg oral dose of Ro70-0004. The primary efficacy endpoint was the duration of rigidity > 60% at the base of the penis measured between 0.5 and 2.5 h post-dose. Rigidity was assessed by penile plethysmography using the RigiScan Plus device during visual sexual stimulation. The safety and efficacy of Ro70-0004 was also assessed. A 50-mg dose of sildenafil was included as a positive control. For the primary efficacy endpoint, the mean duration of erection was 9.69 min following administration of placebo, 8.28 min following Ro70-0004, and 22.64 min following sildenafil. Only the difference between sildenafil and placebo reached statistical significance (P < 0.05). A similar pattern was observed when measuring a duration of rigidity > 80% at the base of the penis (secondary endpoint). Ro70-0004 was safe and generally well tolerated (only two out of 20 patients reported at least one adverse event). The highly selective alpha1A-adrenoceptor antagonist, Ro70-0004, given at a single dose of 5 mg, did not improve erectile function when compared to placebo.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2002

SS-penogram: a new diagnostic test for erectile dysfunction.

The clinical reports on Sildenafil sulfate (Viagra) are mainly based on individual observations. However, there is a paucity of objective studies in the literature. In order to objectively examine the effect of Sildenafil, a SS (Sexual Stimulation)-Penogram that is a non-invasive, simple and physiologic method was developed using a radioisotope (RI). One hundred and four SS-penograms were performed on patients who had a documented erectile dysfunction (ED) lasting for more than 6 months. After an intravenous injection of 99mTc-RBC (15 mCi), the first penogram was taken immediately after sexual stimulation, which was done by 30 minutes of erotic videotape viewing. Forty minutes after administering 25 to 100 mg of Sildenafil, a second penogram was taken. The characteristics of each penogram were analyzed according to a previously reported method. The results were graded as follows; Type I(normal function; 5 min or more of peak erectile response with an induction period of 1 to 6 min), Type II-A (impossible function type; i.e., showing less than 2 times the basal radioactivity level), Type II-B (the unstable type; showing less than 5 min of peak erectile response), and Type II-C (the delayed type; which showed a delay of more than 15 min after the start of sexual stimulation). The patients were grouped according to their response after Sildenafil administration, and the effect of Sildenafil was assessed by comparing the radioactivity from between 7 to 22 minutes and the changes in the characteristics of the penogram. The mean age of the patients was 44.9 +/- 10.2 (23 - 68) years. In the first penogram, Type I was found in 12 patients, and Type II-A in 14, Type II-B in 73, Type II-C in 1 and a mixed (II-B + C) type was found in 4 patients. A second penogram after Sildenafil administration, showed Type I in 46 patients, and Type II-A in 10, Type II-B in 46 and a mixed type was found in 2 patients. The responses after Sildenafil were categorized as follows: 1) An excellent response group (consisting of 56 patients-53.9%); Those who showed greater than 50% increase in the RI area after Sildenafil treatment. 2) A good response group consisting of (23 patients-22.1%); i.e., those who showed a less than 50% but greater than a 20% increase in the RI area after Sildenafil administration. 3) A borderline group (consisting of 15 patients-14.4%); showing less than a 20% change in the RI area after Sildenafil treatment. 4) non-response group (consisting of 10 patients-9.6%). The therapeutic efficacy of Sildenafil, as determined by the SS-penograms, revealed that there was an augmentation in the erectile capabilities in 76% of men (79/104) but a non-response was observed in 9.6% (10/104). The efficacy of Sildenafil on the SS-penogram did not correlate with the patient's age (p=0.198). It is believed that the SS-penogram can be used to accurately evaluate the natural erectile status in sexual and pharmacological stimulation, and provides the most objective erectile response in any therapeutic trial. Consequently, the primary challenge for any erectile dysfunction remedy is to be able to demonstrate its efficacy. A further evaluation is warranted in the non-response group, which was not based on any severe organic dysfunction.

Adult↗
PubMed2002

Distinct mechanisms implicated in atherosclerosis-induced erectile dysfunction in rabbits.

Ageing and atherosclerosis (ATH) are well-known risk factors for erectile dysfunction (ED). To identify the mechanisms implicated in ATH-induced ED, independently of its ageing-associated component, we studied (i) erectile responses in vivo, and, (ii) endothelium-dependent and independent relaxations of corporal strips from young adult (YAD, n=6), adult (AD, n=6), and cholesterol-fed (ATH, n=8) New-Zealand white rabbits. Measurement of Intima/Media (I/M) ratio on iliac arteries from ATH rabbits determined those with moderate (Mod ATH, 0.5+/-0.3) or severe (Sev ATH, 1.5+/-0.4, P<0.05 Mann-Whitney) atherosclerotic lesions. Erectile responses were reduced in AD compared with YAD rabbits (at 6 V to 10 Hz: 51.6+/-4.6% vs. 57.5+/-1.4%); they were similar in AD and mod ATH rabbits (48.1+/-4.6%) but drastically impaired in Sev ATH rabbits (34.8+/-5.4%, P<0.05, two-way analysis of variance (ANOVA)). Corporal endothelium-dependent and -independent relaxations were comparable in YAD and AD rabbits (maximal relaxation to acetylcholine: 51.3+/-9.5 vs. 56.1+/-9.3%) but decreased in ATH rabbits (37.1+/-1.6%, P<0.001, two-way ANOVA). These results suggest that the mechanisms implicated in ATH-induced ED are distinct from the ageing-related process in rabbits. Thus, future therapeutic targets to treat or prevent ATH-induced ED may include the reduction of the atherosclerotic plaque size or progression, as well as an improvement of the smooth muscle and endothelial reactivity of the corpus cavernosum.

Animals↗
PubMed2003

[Efficacy and safety of PGE1 cream in the treatment of erectile dysfunction].

OBJECTIVES: To evaluate the efficacy and safety of PGE1 cream[Befar, NexMed Pharmaceuticals(Zhongshan) Ltd] on men with ED of various etiologies in China. METHODS: This was a double-blind, randomized (1:1, placebo: PGE1 cream), placebo-controlled clinic study of PGE1 cream performed at Peking University Pepole's Hospital for 8 weeks. A total of 42 subjects suffered from erectile dysfunction of psychologic, organic or mixed etiology were screened and randomized, and visited occurred at weeks -4, 0, 2 and 4 weeks covering a 4-week no treatment run-in period and a 4-week period of double blind treatment. RESULTS: At week four PGE1 cream was shown to be significantly (P < 0.01) effective over placebo in the sexual function endpoints analyses. The primary efficacy variables (Questions 3 and 4 from IIEF) revealed a statistically significant (P < 0.01) improvement over placebo along with a clinical efficacy change score with an effective rate of 63.16% on PGE1 cream vs 9.52% on placebo. The secondary efficacy variables supported the conclusion of the primary efficacy (assessing the proportion of successful attempts at sexual intercourse 68.42% on PGE1 cream vs 19.05% on placebo), and the global assessment question (treatment had improved their erections, 73.68% on PGE1 cream vs 19.05% on placebo). PGE1 cream was well tolerated when given prn. Subjects in the study had a low discontinuation rate (4.76%), only one subject (2.38%) discontinued due to adverse events. The incidence of adverse events was higher for PGE1 cream (30.00%) than for placebo (4.76%). The common adverse events were mild pain of penis and urethra. CONCLUSIONS: PGE1 cream is an effective, safe and well-tolerated treatment in subjects with erectile dysfunction of organic, psychologic or mixed etiology.

Adult↗
PubMed2004

Discovery of 2-(4-pyridin-2-ylpiperazin-1-ylmethyl)-1H-benzimidazole (ABT-724), a dopaminergic agent with a novel mode of action for the potential treatment of erectile dysfunction.

A new class of agents with potential utility for the treatment of erectile dysfunction has been discovered, guided by the hypothesis that selective D4 agonists are erectogenic but devoid of the side effects typically associated with dopaminergic agents. The lead agent 2-(4-pyridin-2-ylpiperazin-1-ylmethyl)-1H-benzimidazole (1, ABT-724) was discovered by optimization of a series of benzimidazole arylpiperazines. This highly selective D4 agonist was found to be very potent and efficacious in vivo, eliciting penile erections in rats at a dose of 0.03 micromol/kg, with a positive response rate of 77% erectile incidence. Even at high doses, it was devoid of side effects in animal models of central nervous system behaviors, emesis, or nausea. The structure-activity relationship of the parent benzimidazole series leading to 1 is described, with the detailed in vitro and in vivo profiles described. Distinctive structural features were discovered that are associated with D4 selective agonism in this series of analogues.

Animals↗