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Medical research on sildenafil
Pharmacol Res. 2008 May 21;
Aboutabl ME, Raafat M, Maklad YA, Kenawy SA, Din AG
The association of erectile dysfunction (ED) with cardiovascular diseases is so common. This study was carried out to investigate possible impact of sildenafil; the prototype phosphodiesterase 5 inhibitor used for treatment of ED, on the beneficial hemodynamic and histopathological effects of the prototype third generation calcium antagonist, amlodipine, in nitric oxide (NO)-deficient hypertensive rats. Hypertension was induced by 4-weeks treatment with N(omega)-nitro-l-arginine-methyl ester (l-NAME). Animals were allocated into five groups: normal control, hypertensive control, amlodipine-treated group, sildenafil-treated group and combined treatment group. Drug treatment was started 2 weeks after l-NAME and continued together with l-NAME to the end of the treatment period. Systolic blood pressure (SBP), plasma nitrate/nitrite (NO(x)) and plasma cGMP levels were evaluated at the end of the treatment period. Aortic and renal structural alterations were also investigated. l-NAME treatment caused elevation of SBP, reduction in plasma NO(x) and cGMP levels as well as adverse histological alterations in the tissues studied. Amlodipine normalized SBP, restored plasma NO(x) and cGMP levels and ameliorated the adverse histological changes seen in NO-deficient rats. When combined with sildenafil, both hemodynamic and histopathological effects of amlodipine were augmented with an underlying enhanced elevation of both plasma NO(x) and cGMP levels to statistically higher values than amlodipine alone. These results show that sildenafil augments the beneficial hemodynamic and histopathological effects of amlodipine in NO-deficient hypertensive rats with a pivotal role being played by NO-cGMP pathway. Whether this pharmacodynamic interaction could exist in other models of hypertension that do not share such biochemical derangement warrants further investigations.
Food Addit Contam. 2008 Jul; 25(7): 822-30
Wang J, Chen B, Yao S
A liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method was developed for the simultaneous determination of six synthetic adulterants, namely fenfluramine, phenolphthalein, N-di-desmethyl sibutramine, N-mono-desmethyl sibutramine, sibutramine, and orlistat. The method was applied to the analysis of herbal weight-reducing dietary supplements. Chromatographic separation of the analytes on a C(8) reversed-phase column was achieved using a gradient elution of solvent A: acetonitrile and solvent B: aqueous 20 mM ammonium formate solution. Sildenafil was utilized as an internal standard for quantification. The MS detector was operated in positive electrospray ionization mode. Selected-ion monitoring (SIM) was carried out for m/z 232, 319, 252, 266, 280, 496, and 475 for fenfluramine, phenolphthalein, N-di-desmethyl sibutramine, N-mono-desmethyl sibutramine, sibutramine, orlistat, and sildenafil, respectively. The method was validated for accuracy, precision, linearity, and selectivity. The limits of detection for the six synthetic adulterants ranged from 0.0018 to 0.73 microg g(-1). The proposed method was used for a small survey of 22 dietary supplements of which eleven samples were adulterated with phenolphthalein, N-mono-desmethyl sibutramine, and sibutramine at levels from 0.212 to 96.2 mg g(-1).
J AOAC Int. 2008 May-Jun; 91(3): 580-8
Choi DM, Park S, Yoon TH, Jeong HK, Pyo JS, Park J, Kim D, Kwon SW
Two analogs of sildenafil and vardenafil in food were detected by column liquid chromatography (LC) with a photodiode array detector. They were isolated by preparative LC; their structures were established by mass spectrometry and nuclear magnetic resonance spectrometry. One analog was found to be methisosildenafil (compound A), 5-(5-(3,5-dimethylpiperazin-1-ylsulfonyl)-2-ethoxy-phenyl)-1-methyl-3-propyl-1H-pyrazolo[4,3-d]-pyrimidin-7(6H)-one. It is a sildenafil analog with a dimethylpiperazine ring substituted for the methylpiperazine group. The second analog, hydroxyvardenafil (compound B) is reported for the first time in this study. Hydroxyvardenafil's International Union of Pure and Applied Chemistry name is 2-(2-ethoxy-5-(4-(2-hydroxyethyl)-piperazin-1-ylsulfonyl)phenyl)-5-methyl-7-propyl-imidazo[1,5-f][1,2,4]triazin-4(3H)-one. The novel vardenafil analog has a hydroxyl group added to the ethylpiperazine group.
J Sex Med. 2008 Jun 17;
Melnik T, Soares BG, Nasello AG
Introduction. In contrast to the impressive advances in somatic research of erectile dysfunction (ED), scientific literature shows contradictory reports on the results of psychotherapy for the treatment of ED. Aim. Authors conducted a meta-analysis to evaluate the effectiveness of psychological interventions for the treatment of ED compared to oral drugs, local injection, vacuum devices, or other psychological intervention. Method. Distinct sources of randomized controlled trials (RCTs) were searched: electronic databases (between 1966 and 2007), cross checking of references, and contact with scientific societies. Main Outcome Measures. For dichotomous outcomes the pooled relative risks were calculated and for continuous outcomes mean differences between interventions. Statistical heterogeneity was addressed. Results. Eleven RCTs involving 398 men met the inclusion criteria. Conclusions. There is evidence that group therapy improves ED. Focused sex group therapy showed greater efficacy than control group. Men randomized to receive psychotherapy plus sildenafil showed significant improvement of ED and were less likely than those receiving only sildenafil to drop out. Regarding to the effectiveness of psychological interventions for the treatment of ED compared to local injection and vacuum devices no difference was found.
J Sex Med. 2008 Jun 17;
Jones LA, Klimberg IW, McMurray JG, Padula R, Tseng LJ, Stecher VJ
Introduction. The Sexual Experience Questionnaire (SEX-Q) enables quick and easy assessment of functional, emotional, and satisfaction-related aspects of the sexual experience in men with erectile dysfunction (ED). Aim. To assess correlations between improvement on the SEX-Q and outcomes on other validated questionnaires. Methods. Men with ED (score 60% (and approximately half were >/=80%) of the maximum positive result. Conclusions. SEX-Q change scores correlate with several other functional, emotional, and satisfaction-related outcomes in men treated with sildenafil for ED, allowing a simple and focused evaluation of the sexual experience.
J Sex Med. 2008 Jun 17;
Ponizovsky AM
Introduction. Men with alcohol dependence (AD) commonly suffer from alcohol-induced sexual (erectile) dysfunction (ED) and have poor quality of life (Qol). Knowledge about the factors associated with Qol in such patients is lacking. Aim. To identify in men who sought medical help for both AD and ED the variables that best predicted feelings of satisfaction with life and with specific life domains. Main Outcome Measures. The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Secondary study measures were the International Index of Erectile Function (IIEF), Beck Depression Inventory (BDI-13), General Health Questionnaire (GHQ-12), Rosenberg's General Self-Esteem Scale (RGSES), and the Multidimensional Scale of Perceived Social Support (MSPSS). Methods. Within an open-label sildenafil trial, 101 men aged 18-50 years with an International Classification of Diseases, Tenth Edition diagnosis of AD and concomitant ED were interviewed and completed the questionnaires. Multivariate analyses were applied to establish predictors of life satisfaction and factors mediating the relation between ED and life satisfaction. Results. ED and self-rated depressive symptoms, emotional distress, self-esteem, and perceived social support were found to be significantly associated with Qol and its component domains. Altogether they explained 18-38% of the variance in the Qol ratings. Depressive symptomatology, distress, and self-esteem, individually, demonstrated a mediating effect on the relation between ED and Qol. Finally, self-esteem was shown to be the primary mediator in this relationship. Conclusions. The results of the study show that self-esteem is the primary factor, and depressive symptoms and severe emotional distress are secondary factors mediating the effects of ED on Qol in male patients seeking medical help for both AD and ED. An integrated pharmacopsychosocial approach targeting the underlying ED as well as the mediating emotional conditions could improve Qol of these patients and thus help them to stop using alcohol.
J Nerv Ment Dis. 2008 Jun; 196(6): 496-500
Orr G, Seidman SN, Weiser M, Gershon AA, Dubrov Y, Klein DF
Late onset dysthymic disorder (DD) in middle-aged and elderly men responds poorly to established antidepressants. Previous studies noted an improvement in mood accompanying sildenafil citrate treatment for erectile dysfunction. We sought to evaluate whether sildenafil's mood effects were independent of the effect on erectile function. A 6-week open label study was conducted with 20 male participants, aged 41-60 who were diagnosed with DD and who had normal erectile function. Participants were treated with sildenafil citrate 25 mg per day for 6 weeks. The primary outcome measure was the 21-item Hamilton Depression Rating Scale. Depressive and sexual symptoms were also evaluated using self-report questionnaires. Treatment with sildenafil resulted in a significant reduction in Hamilton Depression Rating Scale mean scores: from 14.61 +/- 3.5 at baseline to 6.39 +/- 5.13 at end of study (F(3,51) = 32.52, p
Med Monatsschr Pharm. 2008 May; 31(5): 162-70; quiz 171-2
Tamborrini G, Distler M, Distler O
Systemic sclerosis (SSc) is a severe fibrotic multiorgan connective tissue disease. Vascular abnormalities such as fingertip ulcers and Raynaud's syndrome as well as involvement of organs including the lungs, heart, kidney and the gastrointestinal tract are prominent features of the disease. There are currently no disease modifying drugs available that can modify the course of the disease. In this review we will discuss medications that have been found to be effective in improving specific organ involvement due to SSc. For the treatment of gastroesophageal reflux disease (GERD), proton pump inhibitors are effective agents. In the setting of clinically significant gastrointestinal dysmotility, metoclopramide, erythromycin and octreotide may be beneficial. Small bowel bacterial overgrowth should be treated with oral antibiotics. Angiotensin converting enzyme inhibitors are the first-line agents for acute renal crisis. A variety of treatment options are available for Raynaud's phenomenon and include calcium channel blockers, iloprost (i. v.), losartan, fluoxetine and sildenafil. Fingertip ulcers can be prevented by using the endothelin receptor antagonist bosentan. The therapeutic options for treatment of pulmonary hypertension associated with SSc include bosentan, sildenafil and various prostacyclin analogs (eg, epoprostenol, treprostinil, iloprost). Sitaxentan, ambrisentan and new phosphodiesterase-5 inhibitors could be new options for therapy as well. Therapeutic options for interstitial lung fibrosis include cyclophosphamide, however, clinical effects are mild to moderate. Methotrexate has been used to treat skin fibrosis and can be beneficial when arthritis is present.
Pulmonary haemosiderosis with juvenile idiopathic arthritis in a Malaysian child.
Med J Malaysia. 2007 Oct; 62(4): 352-4
Wong AR, Noor AS, Rasool AH, Quah BS, Roberton D
A rare case of childhood pulmonary haemosiderosis with juvenile idiopathic arthritis is discussed, with particular reference to treatment with hydroxychloroquine and sildenafil for pulmonary hypertension which occurs secondary to this disease.
Peptides. 2008 Apr 22;
Kandilci HB, Gumusel B, Lippton H
The present study was designed to investigate the effects of rat intermedin/adrenomedullin2 (rIMD), an agonist for calcitonin-like calcitonin receptors (CRLR), on the isolated rat pulmonary arterial rings (PA). When PA were precontracted with 9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F2alpha (U-46619), rIMD (10(-11) to 10(-6)M) induced concentration-dependent relaxation. The pulmonary vasorelaxant response (PVR) to rIMD in PA were completely inhibited by endothelium removal, NG-nitro-l-arginine-methyl-ester (l-NAME), l-N5-(1-iminoethyl)-ornithine hydrochloride (l-NIO) or 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). The PVR to rIMD were also significantly attenuated by a protein kinase inhibitor, Rp-8-bromo-beta-phenyl-1,N2-ethenoguanosine 3':5'-cyclic monophosphorothioate sodium salt hydrate (Rp-8-Br-PETcGMPs), cholera toxin and abolished by tetraethylammonium chloride (TEA), iberiotoxin and precontraction with KCl. The relaxant effect was not affected by 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536), (9S,10S,12R)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy 1H diindolo [1,2,3fg:3',2',1'kl] pyrrolo [3,4-i] [1,6] benzodiazocine-10-carboxylic acid hexyl ester (KT5720), meclofenamate, glybenclamide or apamin. In parallel with SQ22536 and KT5720 results rolipram pretreatment did not alter the rIMD-induced PVR. The PVR to rIMD was potentialized either in the presence of zaprinast or sildenafil. Since the PVR to rIMD was also significantly reduced by rCGRP(8-37) and hADM(22-52) and rIMD(17-47), the present data suggest that rIMD produces PVR by acting in an indiscriminant manner on functional, and possibly different, endothelial CRLR. In conclusion, rIMD stimulates endothelial CRLR are coupled to release of nitric oxide, activation of guanylate cyclases, and promotion of hyperpolarization through large conductance calcium-activated K(+) channels in rat main PA.