Sildenafil is a vasoactive agent used to treat erectile dysfunction and reduce symptoms in patients with pulmonary arterial hypertension (PAH). Sildenafil elevates levels of the second messenger, cGMP, by inhibiting its breakdown via phosphodiesterase type 5 (PDE5). PDE5 is found in particularly high concentrations in the corpus cavernosum, erectile tissue of the penis. It is also found in the retina and vascular endothelium.
Dapoxetine is a selective serotonin reuptake inhibitor, for the treatment of premature ejaculation. In a phase II proof-of-concept study conducted by PPD, dapoxetine demonstrated a statistically significant increase in ejaculatory latency when compared to placebo.
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Erections are controlled by the parasympathetic nervous system. Upon sexual stimulation, a decrease in vascular resistance is mediated by acetylcholine and nitric oxide resulting in vasodilation. The hemodynamic mechanism of an erection is comprised of five stages. During the latent stage, arterial and carvernous smooth muscle relaxation occurs. Vasodilation results in high levels of blood flow causing the penis to grow to its full size. This stage is called tumescence. During the full-erection stage, blood flow fills penis sinusoids and outflow is restricted. This is followed by the rigid-erection phase during which the cavernous muscles contract causing the penis to become rigid. Little blood flow occurs during this stage. During the final stage, detumescence, the cavernous muscles relax and blood flows out of the penis.
Dapoxetine is a selective serotonin reuptake inhibitor currently undergoing trials through Alza (under license from GenuPro, a collaboration between Eli Lilly and PPD). Dapoxetine is a short-acting SSRI drug currently being considered for approval by the Food and Drug Administration (FDA) for the treatment of premature ejaculation in men, which would make it the first drug approved for such treatment. Despite two clinical trials finished in 2006, experts doubt it will be approved by the FDA soon because SSRIs come with undesirable side-effects after long-term use, such as psychiatric problems, dermatological reactions, increase in body weight, lower sex-drive, nausea, headache, upset stomach and weakness, thus not significantly outweighing the benefit of premature ejaculation medication versus the risks.
Mechanism of action
Sildenafil inhibits the cGMP-specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) by sildenafil enhances erectile function by increasing the amount of cGMP.
Dapoxetine mechanism of action is thought to be related to inhibition of neuronal reuptake of serotonin and subsequent potentiation of serotonin activity. The central ejaculatory neural circuit comprises spinal and cerebral areas that form a highly interconnected network. The sympathetic, parasympathetic, and somatic spinal centers, under the influence of sensory genital and cerebral stimuli integrated and processed at the spinal cord level, act in synergy to command physiologic events occurring during ejaculation. Experimental evidence indicates that serotonin (5-HT), throughout brain descending pathways, exerts an inhibitory role on ejaculation.
All medicines may cause side effects, but many people have no, or minor, side effects.Some medical conditions may interact with Sildenafil & Dapoxetine.
Tell your doctor or pharmacist if you have any medical conditions.
Common Sildenafil side effects may include: flushing (warmth, redness, or tingly feeling), headache, dizziness, heartburn, nausea, or upset stomach, abnormal vision (blurred vision, changes in color vision), runny or stuffy nose, nosebleeds, sleep problems (insomnia) or muscle pain, back pain.
Common Dapoxetine side effects: feeling of warmth, fever, muscle aches, redness of the face, neck, arms, and occasionally, upper chest, sore throat, stuffy or runny nose.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.