Mechanism of Action for Erectile Dysfunction and Premature Ejaculation

Dapoxetin > sildenafil and dapoxetine


The most common effects when taking dapoxetine are nausea, dizziness, dry mouth, headache, diarrhea, and insomnia. [16][17] Discontinuation rates due to adverse effects and costs are very high, as demonstrated in a study in Asia which showed that cumulative discontinuation rates within one year are as high as 87%. [18] Unlike other SSRIs used to treat depression, which have been associated with high incidences of sexual dysfunction,[19] dapoxetine is associated with low rates of sexual dysfunction.

Limitations of the study

However, always consult with a specialist in sexual medicine for comprehensive insights. Dapoxetine, under the brand name Priligy, has been patented in the UK, allowing only certain distributors access. However, more affordable generics are expected to surface post-patent expiry (2024), providing a more cost-effective solution. Certain NHS areas do indeed offer Priligy prescriptions. Connecting with a local GP for details on NHS and private prescription options is always advised.

Depression and anxiety

Dapoxetine increases the intravaginal ejaculatory latency time, though exact times can vary based on individual responses. Dapoxetine has undergone placebo-controlled clinical trials, with results indicating a high satisfaction rate. Most men reported an improvement in premature ejaculation symptoms and a reduction in personal distress related to ejaculation. Dr. Srishti Rastogi is a medical writer and healthcare professional dedicated to high-quality patient education and public health awareness.

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Leveraging her clinical background, she produces deeply researched, evidence-based content for digital health platforms and medical publications. Dr. Srishti’s unique dual perspective as a clinician and communicator allows her to craft content that builds trust and credibility with readers navigating sensitive health topics. Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Dapoxetine, sold under the brand name Priligy among others, is a selective serotonin reuptake inhibitor (SSRI) used for the treatment of premature ejaculation (PE) in men ages 18 to 64 years old. Taken as needed, dapoxetine has very mild adverse effects of decreased libido (<1%) and erectile dysfunction (<4%). No case of drug overdose has been reported during clinical trials.

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Many men who have PE also suffer from erectile dysfunction (ED). Treatment for these patients should consider the drug–drug interaction between dapoxetine and PDE5 inhibitors such as tadalafil (Cialis) or sildenafil (Viagra). In Dresser study (2006), plasma concentration of 24 subjects was obtained.

  • Sildenafil is also used in treating certain cases of high blood pressure in lungs.
  • Dapoxetine’s primary goal is to delay ejaculation, increasing sexual confidence.
  • Both drugs are typically prescribed after clinical assessment of sexual health issues.
  • Proper storage of sildenafil and dapoxetine involves keeping away from moisture and heat.
  • Sildenafil can cause visual disturbances as a rare side effect.
  • Dapoxetine may sometimes lead to mood changes or irritability.
  • Both medications are contraindicated with recreational drugs for safety.
  • Sildenafil requires careful dose titration for optimal effectiveness.
  • Dapoxetine’s use is generally limited to short-term management of PE.
  • Patients should report any side effects such as chest pain or severe dizziness.
  • Sildenafil’s absorption can be affected by high-fat meals, delaying effects.
  • Dapoxetine should be ingested with water, on an empty stomach if possible.

Half of the sample pool were treated with dapoxetine 60 mg plus tadalafil 20 mg; the other half were treated with dapoxetine 60 mg plus sildenafil 100 mg. These plasma samples were then analyzed using liquid chromatography-tandem mass spectrometry. The results showed that dapoxetine does not alter the pharmacokinetics of tadalafil or sildenafil.

Volume 2, Issue 4

[3][4][5] Dapoxetine works by inhibiting the serotonin transporter, increasing serotonin's action at the postsynaptic cleft, and as a consequence promoting ejaculatory delay. [6] As a member of the SSRI family, dapoxetine was initially created as an antidepressant. However, unlike other SSRIs, dapoxetine is absorbed and eliminated rapidly in the body. Its fast-acting property makes it suitable for the treatment of PE, but not as an antidepressant. Originally created by Eli Lilly pharmaceutical company, dapoxetine was sold to Johnson & Johnson in 2003 and submitted as a New Drug Application to the US Food and Drug Administration (FDA) for the treatment of PE in 2004.

Why it’s used

[8] Dapoxetine is sold in several European and Asian countries, and in Mexico. In the US, dapoxetine has been in phase III development. In May 2012, US-based Furiex Pharmaceuticals reached an agreement with ALZA Corp and Janssen Pharmaceuticals to market dapoxetine in the United States, Japan, and Canada, while selling the rights to market the drug in Europe, most of Asia, Africa, Latin America, and the Middle East to Menarini. Randomized, double-blind, placebo-controlled buy cheap dapoxetine trials have confirmed the efficacy of dapoxetine for the treatment of PE. [10] Different dosages have different impacts on different types of PE.

Serious side effects

Dapoxetine 60 mg significantly improves the mean intravaginal ejaculation latency time (IELT) compared to that of dapoxetine 30 mg in men with lifelong PE, but no difference is seen in men with acquired PE. [11] Dapoxetine, given 1–3 hours before sexual episode, prolongs IELT and increases the sense of control and sexual satisfaction in men of 18 to 64 years of age with PE. Since PE is associated with personal distress and interrelationship difficulty, dapoxetine provides help for men with PE to overcome this condition. With no drug approved specifically for treatment for PE in the US and some other countries, other SSRIs such as fluoxetine, paroxetine, sertraline, fluvoxamine, and citalopram have been used off-label to treat PE. Waldinger's meta-analysis shows that the use of these conventional antidepressants increases IELT two- to nine-fold above baseline, compared to three- to eight-fold when dapoxetine is used. Alcohol does not affect the pharmacokinetics of dapoxetine when taking concurrently. The mechanism through which dapoxetine affects premature ejaculation is still unclear, but dapoxetine is presumed to work by inhibiting serotonin transporter (SERT) and subsequently increasing serotonin's action at pre- and postsynaptic receptors. [22] Human ejaculation is regulated by various areas in the central nervous system (CNS). These signals are passed on to the brain stem, which then is influenced by a number of nuclei in the brain such as medial preoptic and paraventricular nuclei.

  • Sildenafil enhances erectile function by relaxing smooth muscle tissue.
  • Dapoxetine’s action involves prolonging ejaculatory latency.
  • Both medications are available in tablet form with varying dosages.
  • Sildenafil’s effects last about 4-6 hours, depending on individual factors.
  • Dapoxetine’s onset is usually within 1-3 hours, with effects lasting up to 4 hours.
  • Never double dose of sildenafil or dapoxetine if one dose is missed.
  • Sildenafil should be avoided in patients with cardiovascular conditions without doctor advice.
  • Dapoxetine is not approved for women or children.
  • Patients should inform doctors about any other medications to prevent interactions.
  • Alcohol can diminish sildenafil’s effectiveness and increase side effects.
  • Dapoxetine may require dose adjustment based on response and tolerability.
  • Using both drugs together may enhance sexual performance but increases risk of adverse effects.

[24] Clement's study performed on anaesthetized male rats showed that acute administration of dapoxetine inhibits ejaculatory expulsion reflex at supraspinal level by modulating activity of lateral paragigantocellular nucleus (LPGi) neurons.

  • Sildenafil does not protect against sexually transmitted infections.
  • Dapoxetine does not reduce the frequency of ejaculation but delays it.
  • Patients on nitrate therapy should avoid sildenafil due to severe hypotension risk.
  • Dapoxetine is often used in combination with behavioral therapy for PE.
  • Sildenafil may interact with medications for HIV and other conditions.
  • Dapoxetine’s safety profile is well-established for short-term use.
  • Both medications should be stored safely away from children.
  • Sildenafil can sometimes cause priapism, which requires emergency treatment.
  • Dapoxetine should be discontinued if adverse effects are intolerable.
  • Combining sildenafil with alcohol can worsen hypotensive side effects.
  • Dapoxetine may also cause dry mouth and blurred vision in some users.
  • Regular medical check-ups are recommended during long-term use of these drugs.

These effects cause an increase in pudendal motoneuron reflex discharge (PMRD) latency, though whether dapoxetine acts directly on LPGi or on the descending pathway in which LPGi located is unclear.

What does Priligy do to your body?

[11] However, these SSRIs may need to be taken daily to achieve meaningful efficacy, and their comparatively longer half-lives increase the risk of drug accumulation and a corresponding increase of adverse effects such as reduced libido. [13] Dapoxetine, though, is generally categorized as a fast-acting SSRI. It is more rapidly absorbed and mostly eliminated from the body within a few hours. These pharmacokinetics are more favorable in that they might minimize drug accumulation in the body, habituation, and side effects. Dapoxetine was initially considered unsuccessful in its intended use as an antidepressant; however, it has since been investigated as a possible aid to an approach to depression treatment focused on stress reduction, based on an animal model of depression.

Sildenafil side effects

Dapoxetine should not be used in men with moderate to severe hepatic impairment and in those receiving CYP3A4 inhibitors such as ketoconazole, ritonavir, and telithromycin. Dapoxetine also cannot be used in patients with heart failure, permanent pacemaker, or other significant ischemic heart disease. Caution is advised in men receiving thioridazine, monoamine oxidase inhibitors, SSRIs, serotonin-norepinephrine reuptake inhibitors, or tricyclic antidepressants. If a patient stops taking one of these drugs, he should wait for 14 days before taking dapoxetine. If a patient stops taking dapoxetine, he should wait for 7 days before receiving these drugs. Dapoxetine is a white, powdery, water-insoluble substance. Taken one to three hours before sexual activity, it is rapidly absorbed in the body. Its maximum plasma concentration (Cmax) is reached one to two hours after oral administration. The Cmax and AUC (area under the plasma vs. time curve) is dose dependent. The Cmax and Tm (time needed to obtain the maximum plasma concentration) after single doses of dapoxetine 30 mg and 60 mg are 297 and 498 ng/ml at 1.01 and 1.27 hours, respectively. A high-fat meal does reduce the Cmax slightly, but it is insignificant.

Is Priligy available through the NHS?

The shift from dapoxetine 30 mg to dapoxetine 60 mg should be based on the individual's response and tolerability. The maximum recommended dose should not be exceeded. One must be careful when it comes to combining dapoxetine with other medicines. Dapoxetine and certain recreational drugs, tricyclic antidepressants, or other selective serotonin reuptake inhibitors can interact. Consultation with a healthcare professional is crucial before initiating therapy with multiple drugs.

Cardiovascular safety

Yes, dapoxetine can be taken alongside erectile dysfunction treatments such as sildenafil (Viagra). However, it's vital to be cautious of potential blood pressure fluctuations, as both medications can influence blood pressure. Common adverse reactions include dizziness, headaches, and nausea. To lower these effects, it's advised to: Avoid alcohol, as it can increase specific side effects. Be cautious when standing up from sitting or lying to prevent dizziness.

Clinical monitoring

Grapefruit juice is one of the drinks that might increase the level of dapoxetine in the blood, heightening the risk of side effects. Men with significant ischemic heart disease, sick sinus syndrome, a history of mania or severe depression (major depressive disorder), if already on tricyclic antidepressants, or those with severe renal impairment should avoid taking Priligy. Adverse effects associated with dapoxetine range from nausea, dizziness, and headaches to increased blood pressure. While most of these adverse reactions are mild, it's essential to recognize and report any severe adverse reactions immediately. Clinical trials have not conclusively linked dapoxetine to alterations in testosterone levels. It can be taken with or without food. Dapoxetine is absorbed and distributed rapidly in the body.