How To Erectile Dysfunction Naturally

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Hard On Demand

This informative program was written by Brad Stevens. He had for a long time battled with erectile dysfunctions which lowered his sex drive. He also noticed that he wasn't on sex mood as he was some time back. Even when he and his wife tried having sex, he couldn't sustain an erection to have a satisfactory sex session. He sought all the necessary remedies and out of the comprehensive research he did, he landed into this effective remedy that he is now happy to offer to the people. Brad shares a very informative program whose aim is to educate people about natural solutions of erectile dysfunction. The program has valuable information about Proteins, Amino acids and enzymes that are necessary in this case. Brad wrote this program for men with erectile dysfunctions. It has all the information they need to use a natural remedy for this condition. This program is a downloadable eBook containing everything you would need to treat erectile dysfunctions. Upon purchase, you will get the complete guide with all the ingredients needed and the methods of making the remedy. Read more...

Hard On Demand Summary

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Author: Brad Stevens
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Is Sildenafil for

Sildenafil is a prescription medication that is used to treat erectile dysfunction. It is the first oral medication for this purpose approved by the US Food and Drug Administration. Sildenafil is not an aphrodisiac. It will not arouse or increase sexual desire. It is not a means to improve erections in men who do not have erectile dysfunction. It is not a chemical substitute for working on a relationship. Sildenafil blocks an enzyme in the penis that naturally breaks down a chemical called cGMP, which is produced during sexual stimulation and plays an important role in creating and sustaining normal erections. cGMP allows smooth muscle in the penis to contract, allowing more blood to enter the penis and producing a firmer erection. The longer cGMP remains in the penis, the better the chance of reaching and maintaining an erection. Sildenafil allows more cGMP to remain in the penis, but it does not increase the body's

Does Viagra help with impotence in MS

The physical problem of erectile dysfunction is now openly discussed and is recognized commonly in otherwise healthy men. This change in the public attitude has helped men with MS accept this aspect of sexual function when it occurs and embrace the use of one of the approved drugs for erectile dysfunction. Viagra, Levitra, and Cialis appear to be at least as useful in men with MS as they are in otherwise normal men. Some studies have suggested that these drugs may also Orgasm be helpful in women having difficulty achieving an

Udenafil Erectile Dysfunction [111115

Animal Human Coupling

Udenafil is the fourth in a class of drugs targeting the inhibition of the enzyme phosphodiesterase 5 (PDE5) for the treatment of erectile dysfunction. Inhibition of PDE5 results in the increase in endogenous cyclic guanosine monophosphate (cGMP) concentrations in the penile corpus cavernosum. cGMP induces smooth muscle cell relaxation and subsequent increased blood flow leading to a sustainable erection. Udenafil is a potent antagonist of human PDE5 with an IC50 of 8.25 nM and a comparable selectivity profile as sildenafil for the other PDEs. Unlike ta-dalafil, it does not inhibit PDE11, which has been implicated in myalgia and testicular toxicity. The key steps in the synthesis of udenafil involve the coupling of finally ring closure to build the pyri-midinone ring of the core. In Phase I studies to assess the safety, tolerability, and pharmacokinetics of udenafil, single doses of 12.5-400 mg and multiple doses of 100 and 200mg day were well-tolerated, and exposure increased in a...

Confounding Problems Controlling Drug Costs And Best Drug Selection Owing To Pharmaceutical Company Activities

Direct-to-consumer advertising policy by industry has also indirectly become a problem for therapeutics committees. These advertisements often encourage consumers to demand pricey drugs over cheaper ones that work just as well. The clinicians on the hospital staff then often make similar demands to the therapeutics committee to add the more expensive agents to the formulary. The percentage of industry spending on direct-to-consumer advertising has increased dramatically in the past 10 years. A review of this activity in 2002 by Competitive Media Reporting showed that about 60 of a company's spending on a drug may come from this form of advertising. The major classes of drugs that use this form of advertisement include, in decreasing order, anti-inflammatories, antihistamines, antihyperlipidemics, antiasthmatics, antiulcer drugs, antidepressants, erectile dysfunction drugs, weight loss drugs, oral contraceptives, genital herpes drugs, toenail fungus agents, and hormones. It is...

Executive Functions and the Brains Signaling System

Those who care about persons with ADD and witness their poor performance in important tasks routinely prod them to deal with their impotence in the face of those tasks by insisting Just make yourself do it We can all see that you have the ability. It's just a matter of realizing what is really important and exercising willpower Alternatively, they may impose punishments on the person with ADD or shame them for their failure to make themselves do consistently what they ought to do. These critics seem to assume that the person with ADD needs only to speak emphatically to the conductor of their own mental operations to get the desired results.

Why Has The Person Come For A Checkup

Your initial questions should identify why the person has come for a check-up. Be aware that there may be a subtext to their visit careful listening will help you identify if there are other concerns (Law & McCoriston, 1996 Presswell & Barton, 2000). These may include sexual dysfunction therefore follow up throwaway lines or ambiguity - 'So does this cause impotence ' Your response may be 'Is impotence or problems with having sex worrying you '

Family Medical History

'In your family - that is, your parents, brothers and sisters - are there any health problems that seem to run through the family ' You may prompt with suggestion such as diabetes, hypertension, and skin problems. This gives you information about predisposition, especially with diabetes and skin problems, and helps with differential diagnosis and may be a contributing factor in the reason for the visit, as for example with impotence or recurrent vaginal candidiasis.

Complications and Management

Complications following abdomino-perineal resection have been reported as high as 61 (8). Most of these can generally be prevented by appropriate pre-operative evaluation and careful operative technique. Postoperative sexual dysfunction can occur in both men and women, including a significant percentage of men with impotence. These complications are more common with advancing age and are somewhat unavoidable. Management, when indicated, can consist of counseling, medication, and implantation of prosthetic devices, or reconstructive surgery. The problems of colostomy management are discussed in detail in Chapter 15.

Multiple System Atrophy

The predominant loci of nerve cell loss vary across the MSA subtypes, but with overlap, and they are associated with the prominent but overlapping clinical features, including speech and language findings. Thus, in striatonigral degeneration (MSA-P) nerve cell loss and gliosis predominate in the neostriatum and substantia nigra parkinsonian features, including hypokinetic dysarthria, are prominent and beneficial response to levodopa is limited because striatal neurons containing dopamine receptors are lost. In OPCA (MSA-C), there may be prominent involvement of the cerebellum, explaining clinical cerebellar features, including ataxic dysarthria. In Shy-Drager syndrome, early and prominent dy-sautonomia (including orthostatic hypotension, incontinence, reduced respiration, and impotence) stems from loss of preganglionic sympathetic neurons in the intermediolateral horns because the sub-stantia nigra, striatum, cerebellum, and corticospinal tracts are also affected, parkinsonism...

PNS of the Peripheral Nervous System

Paraneoplastic autonomic neuropathy is primarily seen with SCLC 103 . Lymphoma, non-small cell lung cancer, and ovarian cancer are also associated with autonomic disturbances 104 . Autonomic dysfunction affects 23-30 of Hu antibody positive patients 36, 98 and is the predominant symptom at presentation in up to 9 of the patients 90 . The onset of symptoms is usually subacute. A prominent clinical manifestation in patients with paraneo-plastic autonomic neuropathy is gastrointestinal dysmotility and intestinal pseudo-obstruction, which can occur as part of the PEM SN syndrome or as the sole symptom of Hu antibody related PNS. Ortostatic hypotension and erectile dysfunction are other common features 37, 105, 106 . Autonomic neuropathy is also commonly associated with the CRMP-5 antibody and have been detected in more than 30 of CRMP-5 antibody positive patients 30 . Finally, autonomic dysfunction is a common feature of LEMS with and without malignant disease. In LEMS patients, the most...

How does MS affect sexual function

The most common sexual problem affecting both men and women in good health is the lack of libido (sexual interest or sexual drive). Psychologic stress arising from interpersonal relationships and work is probably the most common single cause for this it is obviously much more of an issue in young adults affected by a major health problem. The resultant uncertainties that naturally arise in these situations contribute to this greatly. The actual diagnosis of illness may induce acute stress, which can precipitate sexual difficulty or aggravate a pre-existing sexual problem. In both men and women with MS, the loss of a feeling of well-being contributes to sexual dysfunction, whether accompanied by a depressed mood or not. Studies have shown that a caring, understanding relationship between the sexual partners is the single most important factor in maintaining good sexual health. It is important to be aware that the use of drugs for erectile dysfunction does not increase libido. Decision...

New Therapies From Existing Drugs

History is replete with examples of compounds that were originally developed for one disease and subsequently found to be beneficial in another. In contrast to the hypothesis-driven philosophy of modern drug discovery, many highly successful new treatments have been discovered by serendipity 3,5,12-14 . The phosphodiesterase (PDE-5) inhibitor, sildenafil for example was originally developed as a potential anti-angina therapy but was observed during early clinical trials to be efficacious for male erectile dysfunction, for which it was subsequently first approved. Further studies on sildenafil have expanded its label to include approval for pulmonary arterial hypertension. The alpha-2 adrenergic agonist, brimonidine, was originally synthesized as an anti-hypertensive and later discovered and marketed as an anti-glaucoma agent. Further examples of drugs with unexpected benefits beyond their initially approved indications include bupropion, which is approved as a smoking cessation drug,...

Brain Imaging Studies Show Stimulants in Action

In other words, increased dopamine in the synapse can act almost as a kind of Viagra to encourage the brain's response to the task. Thus MPH may counter the chronic problem with motivating oneself to do necessary, but not intrinsically interesting, tasks. In this way stimulant medication may help to alleviate the problems described in Chapter 1 as impotence of the mind.

Symptoms And Signs

ATL is associated with acute infiltration of skin and visceral tissue with monoclonal proliferation of CD4 bearing T-lymphocytes. Clinical manifestations include skin lesions due to infiltrating leukaemic cells, interstitial pneumonia, hepatosplenomegaly and bone lesions. The entity of HAM or TSP is characterized by insidious onset and neurological findings of weakness, spasticity of the extremities, hyperreflexia, positive Babinski's sign, urinary and faecal incontinence, impotence and mild peripheral sensory loss. The disease is chronic and within 10 years 30 of patients are bedridden. Nevertheless, cognitive function remains normal.

Multiple Endocrine Neoplasia Type

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant cancer syndrome that features tumors of the parathyroid, pituitary, and the islet cells of the pancreas. These tissues are part of the endocrine system, which produces and secretes various hormones. In response to different hormones, target cells control homeostatic processes, growth, development, and stress. Specifically, with regard to the sites of the MEN1 tumors, the parathyroid glands control levels of calcium and phosphate the pituitary glands regulate metabolic activities of other endocrine glands and growth and the pancreatic islet cells maintain blood glucose concentration. Depending on the site and the extent of the MEN1 tumors, symptoms may include excess calcium in the bloodstream (hypercalcemia), which causes kidney stone formation low blood sugar concentration (hypoglycemia), resulting in dizziness, confusion, weight loss, and glucose intolerance and disruption of the pituitary gland, accompanied by...

Anabolic Androgenic Steroids

Anabolic-androgenic steroids have the same effect on the brain as natural testosterone. Thus, when steroid levels are high, the brain and pituitary gland stop producing the hormones that stimulate sperm production and testosterone secretion. In men, this leads to atrophy of the testes, impotence (inability to achieve or maintain an erection), low sperm count, and infertility. Ironically, anabolic-androgenic steroids have feminizing effects on men and masculinizing effects on women. Men may develop enlarged breasts (gynecomastia), while in some female users the breasts and uterus atrophy, the clitoris enlarges, and ovulation and menstruation become irregular. Female users may develop excessive facial and body hair and a deeper voice, and both sexes show an increased tendency toward baldness. Especially in men, steroid abuse can be linked to severe emotional disorders. The steroids themselves stimulate heightened aggressiveness and unpredictable mood swings, so the abuser may vacillate...

HT2C receptor ligands

There are several noteworthy reports of selective 5-HT2C agonists. The tricyclic furanoindole YM-348 (17), shows good potency for 5-HT2C but only modest selectivity over the closely related 5-HT2A and 5-HT2B receptors (15-fold and 3-fold, respectively) 64 . YM-348 has been shown to be orally active in both the rat penile erection model (typical for 5-HT2C agonists) as well as in reducing weight gain in obese Zucker rats. Three additional potential antiobesity compounds have recently been reported. WAY-629 (18) has been shown to be a potent 5-HT2C agonist with demonstrated oral efficacy in a rat model of feeding behavior 65 . This tetracyclic indole possesses excellent selectivity over a number of monoamine receptor subtypes. The discovery of novel benzazepines as 5-HT2C agonists, with efficacy in an acute feeding paradigm, highlights 19 as a potent (Ki 3nM) ligand with excellent selectivity over the closely related 5-HT2B and 5-HT2A receptor subtypes 66 . The selectivity over 5-HT2B...

Interactions between dopamine and oxytocin in the control of sexual behaviour

Abstract Dopamine and oxytocin are two key neuromodulators involved in reproductive behaviours, such as mating and maternal care. Much evidence underlies their separate roles in such behaviours, but particularly in sexual behaviour. It is generally believed that central dopaminergic and oxytocinergic systems work together to regulate the expression of penile erection, but relatively little is known regarding how they interact. Thus, this review aims to discuss neuroanatomical proof, neuromodulator secretory profiles in the hypothalamus and behavioural pharmacological evidence which support a dopamine-oxytocin link in three hypothalamic nuclei that have been implicated in sexual behaviour, namely the medial preoptic nucleus, supraoptic nucleus and paraventricular nucleus (PVN). We also aim to provide an overview of potential dopamine-mediated transduction pathways that occur within these nuclei and are correlated with the exhibition of penile erection. The PVN provides the most...

Small molecule agonists

Orally bioavailable and more selective against the vasopressin receptors. These have the potential to be drugs where the OT function is compromised, in particular in the treatment of various sexual disorders including the male erectile dysfunction. Additional indications for such compounds could be in promoting labour, controlling post-partum bleeding and increasing milk letdown. In the last few years, there has been an upsurge of interest in the natural neurohypophyseal hormone oxytocin, and new physiological and pathophysiological roles for this peptide have been indicated. During this period, interest has also increased in orally bioavailable oxytocin antagonist and agonists that could be used to treat a range of diseases in addition to the main therapeutic areas of preterm labour, benign prostatic hyperplasia and male sexual dysfunction. In addition, several oxytocin antagonists are being investigated in clinical trials for the prevention of preterm labor and treatment of...

What is the significance of portal pulmonary hypertension How are these patients managed in the pretransplant period

Vasodilators reduce pulmonary artery pressures and prolong survival in some pulmonary hypertension patients. The prostaglandin epoprostenol (Flolan) can reduce pulmonary artery pressures when given as a chronic infusion and has been used to bridge patients to transplantation. Nitric oxide inhaled in doses up to 80 ppm also acutely reduces pulmonary artery pressures in a small number of PPHTN patients and has been used in the operating room to reduce pulmonary artery pressures. More recently, sildenafil (Revatio) has been implemented as an oral agent to reduce pulmonary hypertension in transplant candidates.

Sexual Desire and Aging

Among men, some sexual problems may increase with age, but not necessarily because of aging. The incidence of erectile dysfunction increases for men over 40 and escalates with each decade. The intensity of sexual sensation among men over 40 may be reduced, as may be the speed of erection and the force of ejaculation. Compared with younger men, middle-aged men (45 to 50 years old) are more likely to experience orgasm in one stage, involving a shorter orgasmic period and a rapid shrinking of the erection after ejaculation. The amount of time before another erection can be achieved usually increases, as does the amount of time an erection can be maintained. Among women, biological changes leading to menopause may extend over a 20-year period, with onset generally in the mid 30s and occasionally extending beyond the mid 50s. After menopause, the intensity of sexual response may be reduced, and for some postmenopausal women intercourse may be painful due to vaginal dryness. For many women,...

Disorders of the Bladder and Urethra

Until recently, nearly all men experienced erectile dysfunction after bladder removal surgery, but surgical improvements have reduced the likelihood of this side effect. However, men who have had their prostate gland and seminal vesicles removed no longer produce semen, so they do not ejaculate when they have an orgasm, and they are infertile.

What is the significance of autonomic dysfunction How might you tell if a patient has autonomic dysfunction

Patients with autonomic dysfunction tend to have severe hypotension intraoperatively. Evaluation of changes in orthostatic blood pressure and heart rate is a quick and effective way of assessing autonomic dysfunction. If the autonomic nervous system is intact, an increase in heart rate of 15 beats min and an increase of 10 mm Hg in diastolic blood pressure are expected when changing position from supine to sitting. Autonomic dysfunction is suggested whenever there is a loss of heart rate variability, whatever the circumstances. Autonomic dysfunction includes vasomotor, bladder, bowel, and sexual dysfunction. Other signs include blurred vision, reduced or excessive sweating, dry or excessively moist eyes and mouth, cold or discolored extremities, incontinence or incomplete voiding, diarrhea or constipation, and impotence. Although there are many causes, it should be noted that people with diabetes and chronic alcoholics are patient groups well known to demonstrate autonomic dysfunction.

Are there treatments for loss of genital sensation

A loss of sensation in the genital area can pose problems for both men and women with MS. Fortunately, such a loss of sensation in most patients is usually temporary. In men, the use of Viagra and the other drugs in this group can, in part, overcome erectile dysfunction related to decreased sensation in some cases. Temporary or not, for many women, the use of vibrators can overcome the inability to achieve orgasm. Eros is a specially designed commercially available device to enhance clitoral engorgement and provide stimulation for women who require it. It is important that women consult physicians who are knowledgeable in this area. Generally, gynecologists and sex therapists are better informed than most physicians.

Diagnostic Difficulties And Diagnostic Accuracy

In the tertiary referral setting, the diagnosis of a patient consulting with a history of early falls and visual disturbances can be obvious, however, the diagnosis of PSP may be challenging at early disease stages when the clinician is not familiar with the condition or does not have a high index of suspicion. This is particularly true since, as discussed, individual clinical features of PSP may occur in other parkinsonian or dementia disorders, and telltale signs may present in midstages of the disease. It can be particularly difficult to distinguish PSP from PD during the first 2-3 yr from symptom onset if patients with PSP do not yet clearly exhibit postural instability or ophthalmoplegia, and when they may still show a levodopa response. This presentation is infrequent, but the presence of only axial or additional symmetric limb signs at onset should raise suspicion that the diagnosis of PD may be incorrect. Patients with PD, DLB, or CBD usually have asymmetric signs. In patients...

Phosphodiesterase 5 Inhibitors

PDE5 is widely distributed in smooth muscle, lung and platelets. Inhibitors of PDE5 were originally investigated as antihypertensive and antianginal agents, and their antiplatelet activity is well known (4,5). The advent of the selective PDE5 inhibitor sildenafil (Viagra ) for the treatment of erectile dysfunction (ED), has stimulated tremendous interest in the development of new PDE5 inhibitors, and has provided opportunities to explore new therapeutic applications for PDE5 inhibitors (6). This review will discuss PDE5 inhibitors that are under clinical development for the treatment of ED, as well as advances in the medicinal chemistry of selective PDE5 inhibitors that have been reported over the past year. Reviews have been published describing developments in the medicinal chemistry of PDE5 prior to this time frame and this review will attempt to complement the most recent review of the area (4,7,8). Potential therapeutic indications for PDE5 inhibitors other than for ED will also...

Other Potential Therapeutic Indications

Pulmonary artery vasodilators in animal models of pulmonary hypertension (67). E-4010 (44) is a recently discovered potent, selective and orally active PDE5 inhibitor that has been evaluated in such models (68). Compound 44 (0.1 in diet) was reported to improve mortality of rats with pulmonary hypertension induced by monocrotaline. This outcome was also associated with reduced ventricular hypertrophy and increased lung cGMP levels, but not cAMP levels (69). In chronically hypoxic rats, 44 (0.01 , 0.1 in diet) also attenuated an increase in pulmonary arterial pressure (PAP) without affecting systemic arterial blood pressure, and evoked reductions in ventricular hypertrophy and pulmonary arterial remodeling (70). Sildenafil is under clinical evaluation for the treatment of pulmonary hypertension. In a randomized, double-blind study in healthy adult men, a 56 increase in PAP induced by hypoxia in the placebo treated group was almost completely absent in the sildenafil (100 mg) treated...

Sexual Dysfunction

The mind and the body must work together for normal sexual function. Thoughts and emotions interact with the nervous, circulatory, and endocrine (hormone) systems of the body to produce a sexual response. The sexual response has four stages 2. Arousal (the state of sexual excitement) occurs as blood enters the genital area, leading to an erection in the male.


The term off-target is commonly used in the ADME Tox field. Off-target activity is often referred to as activity of a particular compound toward a target that was not anticipated during the design and that can be beneficial or detrimental (e.g., sildenafil or Viagra, was initially developed by Pfizer to treat angina, but its side effect on male volunteers led to a change in the therapeutic area of the drug). However, this term also means antitarget activity, and binding to antitargets is


Urinary disturbances often appear early in the course of the disease, or are a presenting symptom (impotence common in men). Urinary incontinence (70 of MSA) or retention (30 ) may be detected by medical history, leading to more refined explorations. MSA, PSP, as well as PD patients complain of urgency, frequent voiding, or dysuria. Some describe difficulties voiding but are not aware of chronic urinary retention. Incontinence is never observed in patients with PD and rarely in late stages in PSP. In all cases, additional laboratory tests such as urodynamic tests and sphincter electromyogram (EMG) may make the association between urinary symptoms and urinary tract denervation (13). Patients with PD have less severe urinary dysfunction, by contrast with these common findings in MSA. However, sphincter EMG does not distinguish MSA from PSP.


Drug metabolism occurs primarily in the liver, by the cytochrome P450 (CYP450) enzyme system. When a drug is absorbed through the GI tract, it often undergoes first-pass metabolism. This is where the absorbed drug passes through the liver before being distributed throughout the rest of the body and whilst in the liver, it is metabolised. This process can either activate a drug, as is the case with valaciclovir, or form an inactive metabolite, as with the opioid analgesics. Some metabolites may be toxic and lead to adverse effects. If a drug is heavily metabolised in the liver, it can lead to poor oral bioavailablity, resulting in higher doses being required. Some drugs can inhibit or induce CYP450 enzymes, leading to drug-drug interactions. For example, ritonavir is a potent inhibitor of cytochrome isoenzyme 3A4 thus it can greatly affect the bioavail-ability of other drugs, such as sildenafil.

Facial Expression

The Esthetic Face

A large nose in a man is said to be proof of vitality, sexual potency, courage, and ambition, whereas in women a delicate short nose represents the ideal of beauty. If the mouth is full and large, it reflects sensuality, eroticism, and sociableness, while a small mouth is a sign of a strong will, egoism, and sometimes also of arrogance.

Mc4r Antagonists

Conclusion - Significant progress has been made in the past several years in the development of selective MC4R modulators. In particular, the discovery of small molecule agonists and antagonists will provide the necessary tools to further explore the utilities of these ligands in the treatment of various pathological conditions, including obesity, erectile dysfunction, inflammatory diseases and CNS diseases. Furthermore, these selective tools will allow in-depth evaluation of the melanocortin system and the delineation of the functional roles of different MC receptor subtypes.

Penile Disorders

In some men, the penis becomes curved during an erection. This condition is called Peyronie's disease. The cause is unknown, but fibrous or scar tissue forms inside the penis and causes it to bend at an angle during an erection. This painful condition makes sexual penetration difficult or impossible. The disease often resolves itself over several months. Vitamin E is the first-line treatment for this condition. Injections of corticosteroids into the affected area are sometimes helpful. Ultrasound therapy also has worked for some men. Surgery may cure the disease, but it can cause further scarring and make the condition worse or cause erectile dysfunction. Another rare and not well-understood disease is priapism, a painful, persistent erection not brought on by sexual desire or stimulation. The underlying cause (possibly drugs, blood clots, a tumor in the pelvis or the spine, infection of the genitals, sickle-cell disease, or leukemia) results in blood vessel and nerve abnormalities...


Erectile dysfunction The National Institutes of Health (NIH) defines erectile dysfunction as the repeated inability to get or keep an erection firm enough for sexual intercourse. The word impotence may also be used to describe other problems that interfere with sexual intercourse and reproduction, such as lack of sexual desire and problems with ejaculation or orgasm. Using the term erectile dysfunction makes it clear that those other problems are not involved.

Pde11 Inhibitors

A recent study examined the role of all PDEs and their potential genetic contribution to major depression disorder (MDD). Interestingly, variants in PDE9A and PDE11A were found to be associated with the diagnosis of MDD, while variants in PDE1A and PDE11A were associated with remission on antidepressants. This highlights a potential role for PDE11A in the pathophysiology of MDD. Two recent PDE11 inhibitors, 19 (PDE11A IC50 0.7 nM PDE5 selectivity > 1000-fold) and 20 (PDE11A IC50 3.5 nM > 1000-fold selectivity versus PDE 2, 3, 4, and 5) illustrate compounds structurally unrelated to tadalafil (21) that are active as PDE11 inhibitors 39,40 . Tadalafil has been shown to inhibit PDE11 with an IC50 of approximately 40 nM 41 . These compounds were studied as potential anti-diabetic agents. However, because of their selectivity profiles, they may be useful probes to explore PDE11A biology in the CNS.

Preclinical Studies

ROCK inhibitors have been studied in a variety of preclinical models to assess their potential in non-cardiovascular indications. The use of ROCK inhibitors in a range of diseases including cancer, erectile dysfunction, glaucoma, stroke, pulmonary diseases, and Alzheimer's disease can be found in a number of reviews 8,10-12 .

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