Evaluation and therapeutic regulation of Erectile Dysfunction with visual stimulation test. An objective approach by using Sildenafil Citrate (Viagra) test.

AIM: An objective evaluation of the psychogenic cause of Erectile Dysfunction by performing the visual stimulation tumescence and rigidity (VSTR) test and Sildenafil Citrate (Viagra) test, together with the effectiveness of Sildenafil Citrate (Viagra) medication on impotence caused by different etiologies. MATERIAL AND METHODS: Between 1998 and 2000, a total of 36 men (12 patients with diabetic etiology, 5 patients with vasculogenic risk factor) were enrolled in this study. The mean age of patients was 53 (27-67) years. Following standard questionnaires, including a detailed anamnesis from an andrologic viewpoint, VST was performed in an ambulatory setting and beginning with a test dose of 50 mg. At the end of 2 h, the data was evaluated with computer assistance (Rigiscan device) and if a satisfactory erection had not occurred, an additional second dose of Sildenafil Citrate (Viagra) (50 mg) was given until there was a satisfactory erection. Results obtained from VST: results were classified as group I (fully rigidity, >10 min erection, >70% of rigidity, possible vaginal penetration), group II (unstable erection, 5 min erection, >70% of rigidity, possible vaginal penetration) and group III (tumescence without rigidity, <5 min erection, <70% of rigidity, impossible vaginal penetration). The results obtained during the first 1 h of the VSTR test were regarded as the patient's own erectile condition and later data was accepted as the real effect of Sildenafil Citrate (Viagra). The Fisher exact test was used for statistical evaluation including pre- and post-sildenafil effect on erectile rigidity and duration of erection. RESULTS: The erection status of patients was sufficient in 17 (47.2%) in group I, it was insufficient but sufficient enough with an increased dose of Sildenafil Citrate (Viagra) in 10 (27.7%) in group II, and insufficient without/with full dose of Sildenafil Citrate (Viagra) in 9 (25%) in group III. Considering rigidity and total erectile period, there was a statistical significant difference between the first two groups with respect to the early and late Sildenafil Citrate (Viagra) effects on the VSTR test (p < 0.05). Again, 10 patients with known risk factors (diabetes mellitus 5 and vasculogenic 5) in the second group seemed to give a good response to repeated dosage of Sildenafil Citrate (Viagra) which has been found to be very interesting. However, the rest of the diabetic patients (n = 7) in the third group showed no erection despite the increasing and repeated doses of Sildenafil Citrate (Viagra). CONCLUSION: Sildenafil Citrate (Viagra) with the VSTR test has effective and reliable results which was regarded as very important to diagnose and determine objectively the amount of therapeutic doses in impotence. In accordance with the literature data, our results also confirm the reliability and the practical nature of the VSTR test, which is less time-consuming and cheaper than the nocturnal penile tumescence and rigidity (NPTR) test. In the VSTR test, necessary doses of medication needed for satisfactory erection were easily regulated in patients with certain kinds of impotence. Additionally, self-criticism advantage of the patients on erection and an unnecessary need for regular sexual partners may make this test preferable in the near future. However, we believe that a large group of patients with other definite parameters are certainly needed in order to obtain more reliable data.

Sildenafil Citrate (Viagra) augments sodium nitroprusside-induced but not nitroglycerin-induced hypotension in dogs.

We investigated whether Sildenafil Citrate (Viagra) may reduce the dose of nitrovasodilators to induce deliberate hypotension. Ten mongrel dogs were acutely instrumented with a femoral artery catheter and a pulmonary artery catheter. Sodium nitroprusside (SNP; 1-16 microg. kg(-1). min(-1)) or nitroglycerin (NTG; 2-32 microg. kg(-1). min(-1)) was IV given to induce hypotension. The study consisted of two occasions, in a random order, in each animal: one withSildenafil Citrate (Viagra) pretreatment (1 mg/kg IV followed by 0.3 mg. kg(-1). h(-1)) and the other without to serve as a control. Hemodynamic variables were continuously monitored. Plasma cyclic guanosine monophosphate (cGMP) concentrations were measured by radioimmunoassay. Both SNP and NTG produced dose-dependent decreases in mean arterial blood pressure without affecting the heart rate in the presence as well as in the absence of sildenafil. Systemic vascular resistance index and mean pulmonary arterial pressure were also decreased. The magnitude of mean arterial blood pressure and systemic vascular resistance index reductions caused by SNP was augmented by sildenafil, whereas that caused by NTG was not affected. Neither SNP nor NTG alone altered the plasma cGMP concentrations.Sildenafil Citrate (Viagra) increased the plasma cGMP concentration, which was further increased by SNP but not affected by NTG. These results indicate thatSildenafil Citrate (Viagra) may reduce the dose of SNP in producing deliberate hypotension in the dog. The potentiation of SNP-induced hypotension bySildenafil Citrate (Viagra) may be related to an augmented accumulation of cGMP. IMPLICATIONS:Sildenafil Citrate (Viagra) may reduce the dose of sodium nitroprusside required to induce deliberate hypotension and hence the potential for cyanide toxicity

Determination of transdermalSildenafil Citrate (Viagra) in nude mouse skin by reversed-phase high-performance liquid chromatography.

A simple and sensitive high-performance liquid chromatographic method was developed for the determination ofSildenafil Citrate (Viagra) transdermal permeation of nude mouse skin. A reversed-phase column with UV detection at 224 nm was used for chromatographic separation. The mobile phase consisted of 32% acetonitrile with 0.2% phosphoric acid in water at pH 5.3 adjusted with 10 M NaOH with the flow-rate set at 1.0 ml/min. The limit of quantitation achieved was 5 ng/ml, and the calibration curve showed good linearity over the concentration range of 5-500 ng/ml. The relative standard deviations of within- and between-day analyses were all within 15%.Sildenafil Citrate (Viagra) was found to be stable between pH 3 and 12 during 24-h incubation with skin. After transdermal administration of 15.8 microg/ml ofSildenafil Citrate (Viagra) to nude mouse skin, it was detected as early as 15 min. The transport amount ofSildenafil Citrate (Viagra) could be quantitated and, at pH 8-11, had the highest permeation rate in nude mouse skin

Sildenafil in the treatment of Erectile Dysfunction after radical prostatectomy.

OBJECTIVES: To evaluate the efficacy ofSildenafil Citrate (Viagra) for the treatment of Erectile Dysfunction after radical prostatectomy and to determine whether age, preservation of the neurovascular bundles (NVBs), or the interval between surgery and the initiation ofSildenafil Citrate (Viagra) therapy influences the response to sildenafil. METHODS: We began this study in April 1998, immediately after the Food and Drug Administration approved sildenafil. We surveyed 170 men who had undergone radical retropubic prostatectomy, had not recovered natural erections sufficient for intercourse, and subsequently receivedSildenafil Citrate (Viagra) between 3 and 24 months postoperatively. The data were collected through a confidential mail survey conducted by a clinical nurse. The men used a dose of 50 mgSildenafil Citrate (Viagra) and increased this to 100 mg if they did not obtain an adequate response. RESULTS: In the 120 men who began takingSildenafil Citrate (Viagra) at least 12 months after surgery, the overall response rate was 29%. Results varied markedly by patient age and number of NVBs preserved. In men younger than 55 years in whom both NVBs had been preserved, the response rate was 80%. In contrast, no patient older than 55 years in whom only one NVB had been preserved reported an adequate response. Regardless of age, no patient in whom both NVBs had been excised reported success with sildenafil. Of the 50 patients who began takingSildenafil Citrate (Viagra) less than 9 months after surgery and who had not recovered natural sexual function, none reported erections adequate for intercourse using sildenafil. CONCLUSIONS:Sildenafil Citrate (Viagra) is an effective treatment for men with Erectile Dysfunction after radical retropubic prostatectomy, particularly in younger men in whom both NVBs have been preserved. It is ineffective in men in whom both NVBs have been excised, and it is also ineffective in older men in whom only one NVB has been preserved.Sildenafil Citrate (Viagra) appears ineffective in the first 9 months after prostatectomy

A prospective study comparing paroxetine alone versus paroxetine plusSildenafil Citrate (Viagra) in patients with premature ejaculation.

PURPOSE: We compared the efficacy of paroxetine alone and combined withSildenafil Citrate (Viagra) in patients complaining of premature ejaculation. MATERIALS AND METHODS: Enrolled in this study were 80 consecutive potent men 19 to 47 years old (mean age 34) with premature ejaculation but without any obvious organic cause. Pretreatment evaluation included a history, self-administration of the International Index of Erectile Function (IIEF) questionnaire, physical examination and the Meares-Stamey test to exclude genital tract infection. The initial 40 patients received 10 mg. paroxetine daily for 21 days and then 20 mg. as needed, that is 3 to 4 hours before planned sexual activity, for 6 months (group 1). The other group of 40 men received 10 mg. paroxetine daily for 21 days and then 20 mg. as needed plus 50 mg.Sildenafil Citrate (Viagra) as needed, that is 1 hour before planned sexual activity, for 6 months (group 2). Patients were followed 3 and 6 months after beginning therapy and were evaluated using several general assessment questions, IIEF and ejaculatory latency time. RESULTS: Mean ejaculatory latency time +/- SE in group 1 was 0.33 +/- 0.04, 3.7 +/- 0.10 (p <0.01) and 4.2 +/- 0.03 (p <0.01) minutes at baseline, 3 and 6-month followup, while in group 2 it was 0.35 +/- 0.03, 4.5 +/- 0.07 (p <0.01) and 5.3 +/- 0.02 (p <0.001) minutes, respectively. When improvement in ejaculatory latency time was compared in the 2 groups, group 2 results proved to be significantly greater (p <0.05). Baseline, and 3 and 6-month mean intercourse satisfaction domain values of the IIEF were 9, 11 and 11 (p = 0.09, not significant), and 9, 11 and 14 (p <0.05) in groups 1 and 2, respectively. Group 2 patients reported significantly greater intercourse satisfaction than those in group 1 (p <0.05). At baseline, 3 and 6 months there was a mean of 0.9 +/- 0.1, 1.7 +/- 0.3 (not significant) and 2.5 +/- 0.3 (p <0.01) coitus episodes weekly in group 1, and 1 +/- 0.2, 2.3 +/- 0.3 (p <0.01) and 3.2 +/- 0.1 (p <0.001) in group 2, respectively. Group 2 patients reported a significantly higher number of coitus episodes weekly (p <0.05). Side effects in the 40 group 1 cases included anejaculation in 1 (2.5%), gastrointestinal upset and/or nausea in 5 (12.5%), headache in 4 (10%) and decreased libido in 2 (5%). Side effects in the 40 group 2 cases included anejaculation in 1 (2.5%), headache in 8 (20%), gastrointestinal upset and/or nausea in 6 (15%) and flushing in 6 (15%). Group 2 patients reported significantly more headaches (p <0.01) and flushing episodes (p <0.001) than those in group 1. After 6 months of treatment 33 men (82.5%) in group 1 and 36 (90%) in group 2 were willing to continue therapy (not significant). CONCLUSIONS: Paroxetine combined withSildenafil Citrate (Viagra) appears to provide significantly better results in terms of ejaculatory latency time and intercourse satisfaction versus paroxetine alone in potent patients with premature ejaculation. However, combined treatment is associated with a mild increase in drug related side effects

Dissociable effects of acetylcholinesterase inhibitors and phosphodiesterase type 5 inhibitors on object recognition memory: acquisition versus consolidation.

RATIONALE: Phosphodiesterase enzyme type 5 (PDE5) inhibitors and acetylcholinesterase (AChE) inhibitors have cognition-enhancing properties. However, it is not known whether these drug classes affect the same memory processes. OBJECTIVE: We investigated the memory-enhancing effects of the PDE5 inhibitorSildenafil Citrate (Viagra) and AChE inhibitors metrifonate and donepezil in the object recognition task to find out whether acquisition or consolidation processes were affected by these drugs. METHODS: The object recognition task measures whether rats remembered an object they have explored in a previous learning trial. All drugs were given orally 30 min before or immediately after learning to study acquisition and consolidation, respectively. RESULTS:Sildenafil Citrate (Viagra) given immediately after the first trial improved the memory performance after 24 h and resulted in an inverted U-shaped dose-effect curve with the peak dose at 3 mg/kg. When given before the first trial,Sildenafil Citrate (Viagra) also improved the memory performance. However, the dose needed for the best performance under this condition was 10 mg/kg, suggesting that the dose-effect curve shifted to the right. This can be explained by the metabolic clearance of the high dose of sildenafil. Donepezil had no memory improving effect when given after the first trial. However, when given before the first trial, a gradually increasing dose-effect curve was found which had its maximum effect at the highest dose tested (1 mg/kg). Likewise, only when metrifonate (30 mg/kg) was given before the first trial did rats show an improved memory performance. CONCLUSION: Our data strongly suggest that PDE5 inhibitors improve processes of consolidation of object information, whereas AChE inhibitors improve processes of acquisition of object information

The presence and function of phosphodiesterase type 5 in the rat myometrium.

OBJECTIVE: Cyclic nucleotide phosphodiesterases (PDEs) are a diverse enzyme group with multiple regulatory properties and wide tissue distribution. Such activity includes cyclic adenosine (cAMP) and guanosine monophosphate (cGMP) breakdown. The type 5 isoform (PDE-5, cGMP specific) is the target of specific antagonists (ie, sildenafil, Viagra). We tested the hypothesis that PDE-5 is present in rat myometrium and modulates myometrial activity. STUDY DESIGN: Full-thickness uterine wall was collected from nonpregnant (n=3) and pregnant Sprague-Dawley rats on days 10 (n=4), 17 (n=6), 22 nonlabor (n=5), and 22 during term labor (TL, n=4). Preterm labor (PTL, n=3) was induced in some animals on day 16 with 15 mg/kg mifepristone (RU 486). Tissue samples were prepared for Western blotting using a monoclonal antibody against rodent PDE-5. In a second series, cumulative doses ofSildenafil Citrate (Viagra) (0.005, 0.05, 0.5, 5 mg/kg, intraperitoneal) were administered and the effect on uterine contractility recorded in vivo during term (TL, n=7) and preterm labor (PTL, n=6). Saline solution-injected rats provided temporal control. Uterine contractility was estimated from intrauterine pressure (IP) measured electronically with a sensor tip pressure catheter. Heart rate was recorded simultaneously using electrodes attached to the chest and connected to the same data acquisition system. RESULTS: PDE-5 immunoreactivity was present in the nonpregnant rat uterus and at all gestational times studied, although the expression was unaffected by either pregnancy or the state of labor (preterm or term). A dominant antibody-specific band was identified at 86 kd in the uterine samples, contrasting with lung where the 100-kd PDE-5 isoform was most abundant. Two additional lower molecular weight (55 and 32 kd) bands were also identified as antibody specific. Despite the lack of change in PDE-5 during pregnancy,Sildenafil Citrate (Viagra) reduced IP during TL and PTL beginning at 0.5 mg/kg. The highest dose ofSildenafil Citrate (Viagra) reduced IP during both TL and PTL by 45% and 59% of baseline, respectively (two-way analysis of variance, P<.01). This effect was not accompanied by changes in heart rate. CONCLUSION: PDE-5 is constitutively present in the rat uterine wall. There was no observed change in the PDE-5 protein expression throughout pregnancy. In contrast to the lung, the uterus expresses an 80-kd PDE-5 isoform.Sildenafil Citrate (Viagra) in pharmacologic doses inhibits mechanical uterine activity and might be of benefit if selectively used for treatment of preterm labor

Sildenafil augments pelvic nerve-mediated female genital sexual arousal in the anesthetized rabbit.

The NO-cGMP pathway has been implicated in clitoral and vaginal smooth muscle relaxation based on previous immunochemical, biochemical and physiologic studies. There are limited data from in vivo studies demonstrating enhancement of the genital sexual arousal response by pharmacologic agents influencing the NO-cGMP pathway. The goal of this study was to investigate if sildenafil, a phosphodiesterase type-5 inhibitor, facilitated female genital sexual arousal in an animal model in response to pelvic nerve stimulation (PNS). Using female New Zealand White rabbits, we measured the following parameters before, during and after PNS at 4, 16, and 32 Hz: a) hemoglobin concentration and oxygen saturation in female genital (vaginal, labial, clitoral) tissues by laser oximetry; b) clitoral blood flow by laser Doppler flowmetry; c) vaginal luminal pressure by a balloon catheter pressure transducer; d) vaginal lubrication by tampon.Sildenafil Citrate (Viagra) was administered intravenously (0.21 microg/kg, 0.42 microg/kg, 2.1 microg/kg) to achieve a systemic concentration of 5, 10 and 50 nM, respectively. After 20 minutes, physiologic measurements were repeated.Sildenafil Citrate (Viagra) (50 nM) caused a significant increase in genital oxyhemoglobin concentration and a significant decrease in genital deoxyhemoglobin concentration.Sildenafil Citrate (Viagra) also increased the duration of response following PNS, relative to genital hemoglobin concentration and mean clitoral blood flow.Sildenafil Citrate (Viagra) caused a decrease in vaginal luminal pressure and resulted in an increase in vaginal lubrication. These data indicate that the NO-cGMP pathway is involved in the physiologic mechanism of female genital arousal and thatSildenafil Citrate (Viagra) facilitates this response in an in vivo animal model