Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0027497 (nausea)
23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dopamine receptor agonist apomorphine has been recently introduced in the treatment of erectile dysfunction. While it is well established that dopamine D2-like receptors play a crucial role in this effect, conflicting result are reported in the literature as for the role of dopamine D1-like receptors. The aim of this study was to determine the effect of systemic administration of dopamine D1-like receptor agonists on penile erection in rats. Male Wistar rats were treated with three different, and not structurally related, dopamine D1-like receptor agonists: the partial agonists SKF38393 ((+) 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine) and CY 208-243 ((-)-4,6,6a,7,8,12b-exahydro-7-methylindole [4,3-ab]fenantridine), and the full agonist A 77636 ((-)-(1R,3S)-3-Adamantyl-1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1H-2-benzopyran hydrochloride). All three compounds dose-dependently increased the number of penile erections, with the full agonist A77636 showing a more pronounced effect with respect to the other two. Moreover, the dopamine D1-like receptor antagonist SCH 23390 ((R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) dose-dependently antagonised A77636 effect. These results show that systemic administration of dopamine D1-like receptor agonists induce penile erection in rats. This observation suggests that dopamine D1-like receptor agonists might be considered as a possible alternative to apomorphine in the treatment of erectile dysfunction, thus avoiding the typical side effects related to the stimulation of dopamine D2-like receptors such as nausea.
...
PMID:Dopamine D1 receptor agonists induce penile erections in rats. 1253 62

Apomorphine SL (Ixense (TM) ) (apo SL) is a dopamine receptor agonist that can enhance sexual function in patients with erectile dysfunction (ED). For a patient, the ability to achieve a physiological erection, tolerability, efficacy and the speed of onset of the therapy are of considerable importance when considering ED treatment. Recent studies have focused on determining the patient's tolerability to apo SL as a therapy for ED. In addition, the cardiovascular profile of those patients that would be likely to receive apo SL in the clinic has been assessed. These studies have shown that apo SL is safe and effective in the treatment of ED and offers a new therapeutic option for the first-line treatment of patients with different concomitant diseases including cardiovascular disease and diabetes. The most frequently reported adverse events were nausea and dizziness, but no major adverse events have been noted in any of the clinical trials.
...
PMID:Tolerability and safety of apomorphine SL (Ixense (TM) ). 1282 97

The aim of the study was to evaluate the efficiency, after 1 year, of combined use of psychodynamic psychotherapy integrating virtual reality (VR) for the treatment of erectile dysfunction (ED) and premature ejaculation (PE) in 160 heterosexual males who had neither any prior sexual therapy nor had made use (either before, during or after therapy) of any specific pharmaceuticals for the treatment of primary sexual dysfunction. All subjects had given their informed consent. After a clinical diagnosis in an andrologic center, 50 presumably psychological ED (average age 43.7 years), 60 mixed ED (53.9 years) and 50 primary PE (39 years) who suffered these problems over 6 months were undergoing a cycle of 12 sessions, over a 25-week period, of psychotherapy, integrating an audio CD and helmet with miniature television screens that projected specially designed CD-ROM program on the ontogenetic development of male sexual identity. The clinical follow up was done after 6 and 12 months after the cycle. After one year, the overall partial (two times out of three) and complete positive response rate for psychological ED was 75%, for mixed ED was 47% and for PE was 54%. We considered drop-out cases as only before the 7th session of the treatment cycle, the drop-outs after session 7 and the patients that did not show up for follow-up are counted as negative results. Two patients reported nausea and one, vertigo during the first 15-min virtual reality experience. Considering the particular way that full-immersion virtual reality involves the subject who experiences it, we hypothesized that this methodological approach could speed up the therapeutic process. The evidence that positive results persist over time allows us to hypothesize that certain changes in cerebral function can be possible and that these changes are correlated to favorable sexual performance in the male.
...
PMID:Male sexual dysfunctions and multimedia immersion therapy (follow-up). 1285 85

PT-141, a cyclic heptapeptide melanocortin analog, was evaluated following intranasal administration in healthy male subjects and in Viagra-responsive erectile dysfunction (ED) patients. Erectile response was assessed by RigiScan trade mark in healthy subjects without visual sexual stimulation (VSS) and in Viagra-responsive ED patients with VSS. In healthy subjects, mean C(max) and AUC((0-t)) increased in a dose-dependent manner. Median T(max) was 0.50 h and mean t(1/2) ranged from 1.85 to 2.09 h. In both studies, an erectile response induced by PT-141 administration was statistically significant, compared to placebo, at doses greater than 7 mg, with the onset of the first erection occurring in approximately 30 min. PT-141 was safely administered and well tolerated in both studies. A maximum-tolerated dose was not identified. Flushing and nausea were the most common adverse events reported in both studies and no clinically significant changes in vital signs, laboratory tests, ECGs, or physical exams were observed. Based upon its erectogenic potential and tolerability profile, PT-141 is a promising candidate for further evaluation as a treatment for male ED.
...
PMID:Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction. 1496 71

Erectile dysfunction (ED) is more frequent among end-stage renal failure patients than the normal population. Sildenafil citrate has been successfully used for the symptomatic treatment of erectile dysfunction. The aim of this study was to determine the efficacy and safety of sildenafil citrate in the treatment of ED in patients on hemodialysis. Fifty-five hemodialysis patients above 18 years suffering from ED with steady sexual partners were included in the study. The first five and fifteenth questions of the International Index of Erectile Function were employed to evaluate ED in the patient group. A Single 50-mg sildenafil citrate tablet was prescribed for each patient. The patients were encouraged to take it on the day after hemodialysis and 1 hour before sexual intercourse. The erectile function of the patients after the treatment was re-evaluated in the same manner by International Index of Erectile Function. The ages of the patients ranged between 30 and 73 years (mean 50.6 +/- 10.9). The overall response rate was 74.5% (38/51). Side effects were nausea (n = 2), palpitation (n = 2), flushing (n = 1), and angina (n = 1). Sildenafil citrate (50 mg) was observed to be safe and effective for treatment of hemodialysis patients with careful evaluation and proper patient selection.
...
PMID:Efficacy and safety of sildenafil citrate in hemodialysis patients. 1501

Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. Many drugs are now available for the treatment of ED, with oral pharmacotherapy representing the first-line option for most patients. Sildenafil citrate, an inhibitor of the enzyme phosphodiesterase type 5 (PDE5), is the most widely prescribed oral agent and has a very satisfactory efficacy-safety profile in all patient categories. Tadalafil (Cialis; Eli Lilly & Co., ICOS) and vardenafil (Levitra; Bayer Pharmaceuticals, GlaxoSmithKline) are new PDE5 inhibitors that have recently been approved worldwide. Both have been associated with significant positive efficacy-safety profiles. Apomorphine sublingual is a dopamine D1 and D2 receptor agonist, which has been approved for marketing in Europe. It is best selected for treating patients with mild-to-moderate ED, but it is seldom used in clinical practice due to its limited efficacy and side effects, particularly nausea. Patients who do not respond to oral pharmacotherapy or who are unable to use it are appropriate candidates for intracavernosal and intraurethral therapy. The efficacy of second-line treatment is high, but the attrition rate remains significant. For the purpose of this review, clinical and pharmacological analysis focuses on the recent advances in the field of oral therapy, including PDE5 inhibitors and sublingual apomorphine.
...
PMID:Emerging oral drugs for erectile dysfunction. 1515 43

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.
...
PMID: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. 1523 63

Inhibitors of phosphodiesterase type 5 (PDE-5) are well established as an oral treatment for the majority of patients with erectile dysfunction (ED). PDE-5 is found in high concentration in smooth muscle cells of the corpora cavernosa. However, enzymes of the PDE family are also expressed in various other tissues, including the brain. Little is known about its effects on the central nervous system (CNS), although it has been suggested that PDE-5 inhibitors might cross the blood-brain barrier. Side effects, such as headache, nasal congestion, flushing, nausea, are much more common. We describe a patient who had a transient global amnesia (TGA) after his first-ever use of tadalafil, a potent PDE-5 inhibitor. Despite the fact that the aetiology of TGA has not entirely been clarified at present, we consider the hypothesis of a causal relationship as tempting with respect to the current hypotheses of TGA pathophysiology. This case, together with others, suggests that PDE-5 inhibitors might be capable of exerting adverse effects in the CNS. Physicians should be aware of the possibility of neurological disturbances when prescribing PDE-5 inhibitors for ED.
...
PMID:Transient global amnesia after intake of tadalafil, a PDE-5 inhibitor: a possible association? 1567 2

This meeting underscored advances in the exploitation of cyclic nucleotide phosphodiesterases (PDEs) as drug targets. One highlight of the meeting was the disclosure of a new PDE isozyme, bringing to 11 the total number of genetically distinct isozyme families thus far identified. Also reported was the phenotypic characterization of a PDE4D murine genetic knockout. With respect to drug discovery and development, the most encouraging information presented centered on advances in targeting PDE4 with therapeutically useful inhibitors. Historically, the therapeutic utility of isozyme-selective PDE4 inhibitors has been limited by class-associated side effects, namely nausea and dyspepsia. New PDE4 inhibitors are being designed with the specific intent of improving upon the therapeutic ratio of first-generation agents. The profiles of two second-generation PDE4 inhibitors, SB-207499 (Ariflo; Smithkline Beecham plc) and PD-189659, were presented. SB-207499 demonstrated marked efficacy in phase II clinical trials in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD), a disease of very high unmet medical need. PD-189659 has yet to enter clinical trials, but its preclinical profile indicates that this agent can produce substantial anti-inflammatory effects without producing class-associated side effects in animal models. A number of presentations were also given on the utility of PDE5 inhibitors in the treatment of male erectile dysfunction (MED). The widespread use of Viagra (sildenafil; Pfizer Inc) over the last year has reinforced the perception that PDE5 inhibitors are safe and effective agents for the treatment of MED. The overall tenor of the meeting was distinctly upbeat, with most participants believing that PDE isozymes are becoming ever more accessible as targets for drug discovery in a variety of therapeutic areas.
...
PMID:PDE inhibitors--Second William Harvey Research Conference. Drugs with an expanding range of therapeutic uses. 1-3 December 1999, Nice, France. 1610 32

There is now a range of treatments for patients with erectile dysfunction (ED) beyond the psychosexual counselling and surgical implants that were the only available management options for many years. Oral treatments, which are minimally invasive, are the favoured first-line option for treatments and include the phosphodiesterase-5 (PDE5) inhibitors, and dopamine agonists such as apomorphine. Psychosexual counselling may still be an appropriate treatment, on its own or in combination, in a minority of patients who do not respond to oral treatment, or where an origin for the ED is likely from the history. The PDE5 inhibitors, sildenafil, tadalafil, and vardenafil, have proven to be effective and well tolerated and facilitate erectile function. Apomorphine is also effective, but causes nausea in a minority of men. The alpha-receptor antagonist yohimbine has been found to be effective in some placebo-controlled trials, but its effectiveness is probably inadequate for treatment of most ED. Intracavernosal injection of drugs such as prostaglandin E1, papaverine, and phentolamine (sometimes in combination) is an effective but invasive treatment. Other treatments include testosterone, vacuum-pump treatment, surgery, and surgical implants, and tend to be used where patients do not respond to oral treatment and counselling.
...
PMID:Available and future treatments for erectile dysfunction. 1615 22


<< Previous 1 2 3 4 Next >>

---