Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sexual problems are highly prevalent in both men and women and are affected by, among other factors, mood state, interpersonal functioning, and psychotropic medications. The incidence of antidepressant-induced sexual dysfunction is difficult to estimate because of the potentially confounding effects of the illness itself, social and interpersonal comorbidities, medication effects, and design and assessment problems in most studies. Estimates of sexual dysfunction vary from a small percentage to more than 80%. This article reviews current evidence regarding sexual side effects of selective serotonin reuptake inhibitors (SSRIs). Among the sexual side effects most commonly associated with SSRIs are delayed ejaculation and absent or delayed orgasm. Sexual desire (libido) and arousal difficulties are also frequently reported, although the specific association of these disorders to SSRI use has not been consistently shown. The effects of SSRIs on sexual functioning seem strongly dose-related and may vary among the group according to serotonin and dopamine reuptake mechanisms, induction of prolactin release, anticholinergic effects, inhibition of nitric oxide synthetase, and propensity for accumulation over time. A variety of strategies have been reported in the management of SSRI-induced sexual dysfunction, including waiting for tolerance to develop, dosage reduction, drug holidays, substitution of another antidepressant drug, and various augmentation strategies with 5-hydroxytryptamine-2 (5-HT2), 5-HT3, and alpha2 adrenergic receptor antagonists, 5-HT1A and dopamine receptor agonists, and phosphodiesterase (PDE5) enzyme inhibitors. Sexual side effects of SSRIs should not be viewed as entirely negative; some studies have shown improved control of premature ejaculation in men. The impacts of sexual side effects of SSRIs on treatment compliance and on patients' quality of life are important clinical considerations.
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PMID:Effects of SSRIs on sexual function: a critical review. 1127 Sep 25

Sexual dysfunction is highly prevalent in both sexes. Considerable progress has been made in the development of new pharmacologic treatments since the approval of sildenafil in 1998. A variety of oral erectogenic agents are available or are in late-phase development, including centrally active dopamine agonists (e.g., sublingual apomorphine), peripheral nonselective alpha-blockers (e.g., oral phentolamine), and other phosphodiesterase type-5 inhibitors (e.g., vardenafil). These drugs have recently been evaluated for the treatment of female sexual arousal disorder, although results to date have been inconclusive. Pharmacologic therapies have also been proposed for the treatment of premature ejaculation and hypoactive sexual desire disorder. Strong evidence exists for the value of serotonergic drugs (e.g., selective serotonin reuptake inhibitors) in the treatment of premature ejaculation. Further research is needed, particularly on the effects of these drugs on female sexual dysfunction.
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PMID:Sexual pharmacology in the 21st century. 1125 55

Drugs for the treatment of premature ejaculation (PE) are divided to two categories: oral drugs and local drugs. Oral drugs include antidepressive drugs, alpha-adrenoceptor blocking drugs, phosphodiesterase type V blocking drugs and Chinese herbal medicine. Local drugs include local surface drugs, intracavernosal injective drugs and local urethra drugs. Antidepressive drugs are extensively used, which have moderate efficacy, relatively more side effects and high recurrence rate; alpha-adrenoceptor blocking drugs are seldom used and are less effective than antidepressive drugs; phosphodiesterase type V blocking drugs like sildenafil have good efficacy and few side-effects and are worthy to be studied further. Local surface drugs like SS-Cream have good efficacy and few side-effects and are worthy to be applied and promoted; local urethral drugs like MUSE and Befar may become a new method to treat PE after being further studied. Medication for premature ejaculation shall be made specific and suitable as much as for each individual patient.
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PMID:[Medication for premature ejaculation]. 1286 42

Serotonergic drugs (SSRIs) are the most commonly used, but they are characterized by relapse some time after medication interruption as well as by sexual side effects. The efficacy of phosphodiesterase-5 inhibitors seems excellent, but the risk of tachyphylaxis has been reported. The former (fluoxetine, paroxetine, sertraline, clomipramine) should be used in young patients with hyper-orgasmic forms, while the latter (sildenafil, tadalafil, vardenafil) should be used in hypo-orgasmic forms, in old age or when PE is associated with erectile dysfunction. Topical anesthetics provide satisfactory results in premature ejaculation due to hypersensitivity of the glans, and physiotherapy of the pelvic floor muscles proves successful in cases associated with pelvic floor dysfunction. Therapeutic associations and psycho-sexual therapy techniques may improve results, particularly in the long term.
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PMID:Premature ejaculation. 3. Therapy. 1569 39

With phosphodiesterase inhibitors, a safe and effective oral therapy has emerged for erectile dysfunction. Increasing awareness, particularly through the media, is inducing more men to seek help for this condition. Erectile dysfunction is defined as the persistent inability to achieve or maintain an erection adequate for satisfactory sexual activity. The prevalence increases with age. Basic and clinical research is identifying the neurovascular and humoral control of the mechanisms. The initial evaluation should differentiate erectile dysfunction from premature ejaculation and loss of libido. Myocardial insufficiency, hypogonadism and peripheral neuropathy should be looked for. Initial laboratory investigations should be restricted to identifying previously undetected medical illness that may directly contribute to erectile dysfunction. Discussing the available options with the couple is an important aspect. If erectile dysfunction is secondary to other treatable disorders these should be treated simultaneously. When other diseases that require intervention are ruled out and if there are no contraindications, therapy may be initiated with a phosphodiesterase inhibitor. In selected cases, psychosexual therapy may be beneficial. If phosphodiesterase inhibitors are contraindicated, vacuum constriction devices may be tried. Further options include intracavemosal injection, intraurethral instillation, penile revascularization and prosthesis. The availability of effective and well-tolerated oral medications has dramatically changed the clinical approach to erectile dysfunction. Pharmacotherapy is the preferred cost-effective first-line therapy in the vast majority of patients. A stepped-care approach is followed in the primary care and family practice settings. Appropriate urological, endocrine and psychiatric referrals, and shared decision-making with the couple will enable effective treatment of men with erectile dysfunction.
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PMID:Erectile dysfunction. 1643 47

Premature ejaculation is a common sexual problem which presents to genitourinary (GU) medicine services. Five main treatment approaches have been used in clinical trials: behavioural therapy, antidepressants, phosphodiesterase-5 (PDE5) inhibitors, topical anaesthetic agents and alpha-blockers. We have carried out a systematic review of published pharmacological trials. All antidepressants appeared to delay ejaculation to some extent at all doses. Anaesthetic creams appeared to be as successful in slowing ejaculation as antidepressants without systemic side-effects, although some patients did experience erectile problems or unpleasant local symptoms. Anecdotally, behavioural therapy is effective and appears to have long-lasting efficacy. There is a need for quality comparative trial of behavioural therapy, topical anaesthetic agents and antidepressants, including appropriate measures of relapse, follow-up and acceptability of continuing long-term treatment.
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PMID:A review of controlled trials in the pharmacological treatment of premature ejaculation. 1621 10

Premature ejaculation is a common male sexual dysfunction. Treatment modalities as recommended by the British Association of Sexual Health and HIV include behavioural therapy, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) and local anaesthetic creams. We audited the clinical cohort from our dedicated sexual dysfunction clinic to determine the success of prescribed treatment and co-existing prostatitis/male pelvic pain, erectile dysfunction, phosphodiesterase-5 (PDE5) inhibitor use and anxiety. The use of SSRIs was successful in the treatment of premature ejaculation with or without the use of local anaesthetic cream. Co-existing prostatitis/male pelvic pain, erectile dysfunction, PDE5 inhibitor use and anxiety were high.
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PMID:Pharmacological treatment for premature ejaculation. 1621 22

Potential pharmacokinetic interactions between dapoxetine, a serotonin transporter inhibitor developed for the treatment of premature ejaculation (PE), and the phosphodiesterase-5 inhibitors tadalafil and sildenafil, agents used in the treatment of erectile dysfunction (ED), were investigated in an open-label, randomized, crossover study (n=24 men) comparing dapoxetine 60 mg, dapoxetine 60 mg+tadalafil 20 mg, and dapoxetine 60 mg+sildenafil 100 mg. Plasma concentrations of dapoxetine, tadalafil, and sildenafil were determined by liquid chromatography-tandem mass spectrometry. Tadalafil did not affect the pharmacokinetics of dapoxetine, whereas sildenafil increased the dapoxetine AUCinf by 22%; these effects were deemed not clinically important. Dapoxetine did not appear to affect the pharmacokinetics of tadalafil or sildenafil. Most adverse events were mild in nature. Thus, dapoxetine has no clinically important pharmacokinetic interactions with tadalafil or sildenafil, and the combinations are well tolerated.
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PMID:Dapoxetine, a novel treatment for premature ejaculation, does not have pharmacokinetic interactions with phosphodiesterase-5 inhibitors. 1630 8

Premature ejaculation (PE) is a common condition associated with significant adverse effects on the sexual and overall quality of life of men with this condition. Behavioral therapies, such as the "squeeze" and "stop-start" techniques, and psychotherapy, have been the mainstay of PE management for many years. However, evidence of their short-term efficacy is limited while support for their long-term benefit is lacking. There are currently no medications licensed specifically for the treatment of PE. This paucity of pharmacological treatment may, in turn, contribute to the absence of systematic procedures for the identification, evaluation, and treatment of PE patients. Current "off-label" pharmacotherapeutic approaches include topical anesthetics, phosphodiesterase-5 inhibitors, and serotonin reuptake inhibitors. Of these, the serotonin reuptake inhibitors show the greatest efficacy and an increasing body of evidence is illuminating their mode of action. Nevertheless, all current "off-label" pharmacotherapeutic approaches fall short of the ideal therapy for PE. In the absence of a cure, such a treatment should be tolerable, inconspicuously used, effective from first dose, rapid in onset of action, and available as a prn-dosing regimen. It is anticipated that agents in development for the specific indication of PE will come closer to this ideal than existing pharmacotherapeutic approaches.
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PMID:Diagnosis and treatment of premature ejaculation: the physician's perspective. 1642 96

In recent years, late-stage clinical drug development that primarily focuses on urogenital targets has centered around four areas of medical need (both unmet need and aiming to improve on existing therapies). These include male sexual dysfunction (MSD), female sexual dysfunction (FSD), prostatic pathology (neoplastic, pre-neoplastic, and non-neoplastic), and improvement in lower urinary tract symptoms. Despite the regulatory approval of compounds to treat erectile dysfunction (ED), benign prostatic hyperplasia, a number of treatments for overactive bladder, and stress urinary incontinence, there remains a deficiency in addressing a number of conditions that arise out of pathophysiological dysfunction resulting in lower urogenital tract sexual conditions. In terms of late-stage clinical development, significant progress has most recently been made in MSD development, especially in understanding further a common and complex sexual dysfunction--that of premature ejaculation. The search also continues for compounds that improve ED in terms of better efficacy and superior safety profile compared to the currently marketed phosphodiesterase-5-inhibitors. Whilst there are no approved medications to treat the subtypes of FSD, there has been significant progress in attempting to better understand how to appropriately assess treatment benefit in clinical trial settings for this difficult to diagnose and treat condition. This review will focus on late-stage human clinical development pertaining to MSD and FSD.
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PMID:Late-stage clinical development in lower urogenital targets: sexual dysfunction. 1646 80


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