Abstract：
:Phosphodiesterase 5 (PDE5) inhibitors are efficacious in treating patients with erectile dysfunction. New PDE5 inhibitors with different selectivity and pharmacokinetic profiles have been vigorously pursued. Here we report two novel, potent, and selective PDE5 inhibitors, JNJ-10280205 and JNJ-10287069, with Ki values of 0.05 and 0.12 nM, respectively. Both compounds displayed superior selectivity against PDE1-4 and -6 when compared to sildenafil. In the anesthetized dogs, JNJ-10280205 and JNJ-10287069 exhibited similar efficacy as sildenafil in enhancing erectile functions, with no significant effect on cardiovascular parameters. Pharmacokinetic studies showed that JNJ-10287069 had better oral bioavailability than JNJ-10280205 in several animal species. In vitro study suggested that cytochrome P450 (CYP) 3A4 played a major role in the metabolism of both compounds. The compounds inhibited some of the CYP450 enzymes and the human ether-a-go-go (HERG) channel at much higher concentrations than that required to inhibit PDE5, thus, no cross inhibition would be expected at therapeutic doses. Both compounds are suitable clinical candidates.
journal_name
Int J Impot Resjournal_title
International journal of impotence researchauthors
Qiu Y,Bhattacharjee S,Kraft P,Mathew John T,Haynes-Johnson D,Jiang W,Sui Z,Lundeen Sdoi
10.1038/sj.ijir.3901462subject
Has Abstractpub_date
2006-09-01 00:00:00pages
477-83issue
5eissn
0955-9930issn
1476-5489pii
3901462journal_volume
18pub_type
杂志文章abstract：:Sexual dysfunction is a common problem of increasing incidence that is associated with multiple co-morbid conditions and chronic diseases. In heart failure, however, exact numbers are unknown, in part secondary to under-reporting and under-interrogating by health care providers. A gender-specific questionnaire was mod...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/sj.ijir.3901613
更新日期：2008-01-01 00:00:00
abstract：:Multiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by parkinsonism and cerebellar, autonomic, urinary, and/or pyramidal dysfunction. Urinary and erectile dysfunction (ED) symptoms are prominent early features in men with MSA. Autonomic failure, considered until recently to be the ca...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/sj.ijir.3901014
更新日期：2003-08-01 00:00:00
abstract：:The human T-lymphotropic virus type I (HTLV-I) is a retrovirus associated with a chronic myelopathy known as HTLV-I-Associated Myelopathy or Tropical Spastic Paraparesis (HAM/TSP). The main objective was to assess the frequency of erectile dysfunction (ED) in HTLV-I-infected individuals from Salvador and other cities ...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/sj.ijir.3901335
更新日期：2005-07-01 00:00:00
abstract：:In a study on the diagnosis and treatment of erectile dysfunction (ED) in general practice, a self-selected sample of 90 general practitioners (GPs) (76 males, 14 females) from a predominantly urban population of 525 GPs were interviewed. It appeared that 59% would not actively interrogate a patient when an erection p...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：
更新日期：1994-06-01 00:00:00
abstract：:Sildenafil citrate has been shown to be effective in a wide range of patients with erectile dysfunction and has been approved in the United States for this indication. The overall clinical safety of oral sildenafil, a potent inhibitor of phosphodiesterase type 5, in the treatment of erectile dysfunction was evaluated ...
journal_title：International journal of impotence research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1038/sj.ijir.3900354
更新日期：1998-06-01 00:00:00
abstract：:The authors created the glans penis augmentation by injectable hyaluronic acid gel and reported the 6-month result for premature ejaculation. In a total of 38 patients, long-term effects of 5 years were compared to those of 6 months in terms of residual volume of implants and efficacy on premature ejaculation. Maximal...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/ijir.2008.26
更新日期：2008-07-01 00:00:00
abstract：:Modulation of the adrenergic activity and interfering with channels such as potassium channels may affect relaxation and contraction of the corpus cavernosum. Sildenafil is a selective phosphodiesterase-5 inhibitor, proven effective in treating erectile dysfunction. In this study, the effect of sildenafil citrate on a...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/sj.ijir.3901590
更新日期：2007-11-01 00:00:00
abstract：:Non-surgical treatment of Peyronie's disease (PD) has come a long way since it was first described in 1743. A myriad of treatment options are currently available, including oral, intralesional and external energy therapies. The purpose of this article is to review the contemporary literature on non-surgical therapies ...
journal_title：International journal of impotence research
pub_type： 杂志文章,评审
doi：10.1038/ijir.2011.45
更新日期：2012-01-01 00:00:00
abstract：:The imbalance between vasoconstrictors and vasodilators may play an important role in the pathogenesis of erectile dysfunction (ED). A total of 36 patients with ED, organogenic [diabetic (n=12) and nondiabetic (n=12)] and psychogenic (n=12) etiology, and 12 healthy adult men as controls were included. The levels of en...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/sj.ijir.3901059
更新日期：2003-12-01 00:00:00
abstract：:Research in the field of erectile function and dysfunction has continued to expand rapidly. Based on the information available, some directions for future erectile dysfunction therapies can be identified. The first direction is improvement of current therapeutic principles. A second generation of orally active phospho...
journal_title：International journal of impotence research
pub_type： 杂志文章,评审
doi：10.1038/sj.ijir.3900797
更新日期：2002-02-01 00:00:00
abstract：:Penile erection is a vascular phenomenon that results from smooth muscle relaxation, arterial dilation and venous restriction. The atherosclerosis of the penis that occurs with aging causes a decrease in penile oxygen tension. A reduction of smooth muscle cells has been demonstrated in relation with this change in oxy...
journal_title：International journal of impotence research
pub_type： 杂志文章,评审
doi：10.1038/sj.ijir.3900792
更新日期：2002-02-01 00:00:00
abstract：:In order to assess the effectiveness of sildenafil under routine conditions of use in primary care settings and to evaluate its impact on patient's life satisfaction and partner's satisfaction with treatment for erectile dysfunction (ED), an open, multicentre, observational, prospective study was designed in which 281...
journal_title：International journal of impotence research
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1038/sj.ijir.3900782
更新日期：2001-12-01 00:00:00
abstract：:Chronic hypoxia is related to many pathological conditions: aging, heart and respiratory failure, sleep apneas, smoke, chronic obstructive pulmonary disease (COPD), diabetes, hypertension and arteriosclerosis, all characterized by reductions of sleep-related erections (SREs) and by erectile dysfunction (ED). Sleep-rel...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/sj.ijir.3901560
更新日期：2007-09-01 00:00:00
abstract：:The activation of cavernous local renin-angiotensin system has an important role in pathogenesis of diabetic erectile dysfunction (ED). In our primary study, we found that angiotensin Type 1 receptor blocker improved the erectile function of diabetic rats. Therefore we explored the losartan in clinical treatment for d...
journal_title：International journal of impotence research
pub_type： 杂志文章,随机对照试验
doi：10.1038/ijir.2012.4
更新日期：2012-11-01 00:00:00
abstract：:The aim of the present study was to investigate which PD specific factors (e.g., degree of penile curvature, levels of pain) cause most distress and to further explore whether there are specific subgroups of patients that report particularly high levels of psychological distress. Data were available for N = 119 men wi...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/s41443-018-0029-3
更新日期：2018-08-01 00:00:00
abstract：:Experimental models to study the effect of agents on penile erection usually include electrical stimulation of peripheral nerves in anesthetized animals combined with systemic or intracavernous injection of drugs. The objective of this study was to demonstrate that conscious rabbits can be used as a simple and quantit...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/sj.ijir.3900703
更新日期：2001-08-01 00:00:00
abstract：:Between December 1996 and December 1998, 79 inflatable penile implant insertions have been performed at our institution by a single surgeon. The objective of this analysis was to compare our in-patient and out-patient experience with penile prosthesis insertion with respect to ease of performance and complication prof...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/sj.ijir.3900695
更新日期：2001-10-01 00:00:00
abstract：:The clinical profile for apomorphine sublingual (SL), a new centrally active agent for the management of the erectile dysfunction (ED) patient, is described in this article. Apomorphine SL is shown to be rapid in onset (71% of patients within 20 min) with a consistent, predictable response that is independent of sever...
journal_title：International journal of impotence research
pub_type： 杂志文章,评审
doi：10.1038/sj.ijir.3900721
更新日期：2001-08-01 00:00:00
abstract：:The majority of medical students and medical healthcare providers do not feel comfortable when addressing sexual problems. It was suggested that more courses in sexual health are needed at medical schools to overcome this shortcoming. To assess medical students' interest in and attitude about sexual health education a...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/ijir.2016.25
更新日期：2016-09-01 00:00:00
abstract：:The aim of this study was to report feasibility, benefit and complications of superselective transcatheter autologous clot embolizations and duplex sonography-guided compression therapy in four patients with delayed post-traumatic high-flow priapism. Medical records of four consecutive patients diagnosed with delayed ...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/sj.ijir.3901373
更新日期：2006-03-01 00:00:00
abstract：:The single most important factor in the reduction of penile implant infections has been the infection retardant coatings. Virtually every inflatable penile prosthesis (IPP) sold for the last 15 years in America has been coated and the device infection rate has dropped over 50% to less than 1% in experienced implanter ...
journal_title：International journal of impotence research
pub_type： 杂志文章,评审
doi：10.1038/s41443-020-0338-1
更新日期：2020-08-07 00:00:00
abstract：:Erectile dysfunction is a common disorder. However, not all dysfunctional men want to pursue evaluation. To delineate the characteristics of men interested in evaluation of erectile dysfunction, we conducted a mailed survey of 1031 randomly selected male veterans aged 30-99 years. We received 427 completed surveys. Us...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:Several self-injection devices have been recently proposed as an aid to home intracavernosal self-injection treatment for erectile dysfunction, with the purpose of allowing an easier drug administration, decreasing the artificiality of intracavernosal pharmacotheraphy, with the overall goal of increasing the acceptabi...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:Sildenafil has had a dramatic influence on the field of sexual medicine over the past 20 years. Not only have phosphodiesterase-5 (PDE5) inhibitors improved the treatment of erectile dysfunction (ED), they have indirectly contributed to the treatment of male factor infertility. A review of the literature between 1998 ...
journal_title：International journal of impotence research
pub_type： 杂志文章,评审
doi：10.1038/s41443-018-0067-x
更新日期：2019-03-01 00:00:00
abstract：:Considering the presence of dopaminergic receptors in the lumbosacral spinal cord, we tested whether apomorphine could exert a proerectile effect by acting at the spinal level. Intracavernous (ICP) and blood pressures (BP) were measured in anesthetized rats. ICP rises were quantified (duration, percentage of ICPmaximu...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/sj.ijir.3900654
更新日期：2001-04-01 00:00:00
abstract：:Our interim analysis of a phase II clinical trial on low-intensity extracorporeal shockwave therapy (Li-ESWT) for men with erectile dysfunction (ED) has demonstrated it is safe with no reported adverse outcomes. Interim analysis has demonstrated Sexual Encounter Profile 3 (ability to maintain erection till completion)...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/s41443-019-0115-1
更新日期：2019-05-01 00:00:00
abstract：:In several studies we have recently demonstrated that orgasm induces prolactin secretion in healthy males and females. This suggests that prolactin may form a feedback regulator of the refractory period following orgasm. To examine this position we investigated the prolactin response of a healthy multi-orgasmic male s...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/sj.ijir.3900823
更新日期：2002-04-01 00:00:00
abstract：:During penile pharmacotesting, anxiety may overcome complete smooth muscle relaxation and lead to false positive diagnosis of organic male erectile dysfunction (ED). We tested the efficacy and safety of re-dosing of PGE1 alone versus combination of PGE, and the alpha1,2-blocker phentolamine (PHE) to improve an incompl...
journal_title：International journal of impotence research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1038/sj.ijir.3900477
更新日期：2000-02-01 00:00:00
abstract：:The aim of this study was to evaluate changes in men's sexual function after percutaneous transluminal coronary angioplasty (PTCA) treatment for acute myocardial infarction (MI). Sixty men aged 18-70 years old were included in the study. All patients had acute MI and underwent PTCA. They underwent two post PCTA visits...
journal_title：International journal of impotence research
pub_type： 杂志文章
doi：10.1038/ijir.2017.11
更新日期：2017-07-01 00:00:00
abstract：:The diagnosis and classification of female sexual disorders has undergone significant changes over the last fifty years as a function of changing societal expectations for female sexual conduct, available knowledge about sexual psychophysiology and actual clinical practice. Currently, female sexual disorders are conce...
journal_title：International journal of impotence research
pub_type： 杂志文章,评审
doi：10.1201/b14618-47
更新日期：1998-05-01 00:00:00
