- All
- Product Name
- Product Keyword
- Product Model
- Product Summary
- Product Description
- Multi Field Search
 |
100 Tablets
▎Tadalafil Research
What is the research background of Tadalafil?
Research Basis of Erectile Dysfunction: Erectile dysfunction is a common male sexual dysfunction disease, and its pathogenesis is relatively complex, involving the coordinated action of multiple systems such as the nervous, vascular, and endocrine systems. With the in-depth study of the physiological mechanism of penile erection, it has been found that the nitric oxide (NO) - cyclic guanosine monophosphate (cGMP) signaling pathway plays a key role in the process of penile erection. When sexual stimulation causes the release of NO, NO activates guanylate cyclase, increasing the level of cGMP, which leads to the relaxation of the smooth muscles in the corpus cavernosum of the penis, allowing blood to flow into the penis and resulting in an erection. Phosphodiesterase 5 (PDE5) is the main enzyme that degrades cGMP. Excessive activity of PDE5 will lead to a decrease in the level of cGMP, affecting penile erection.
Research and Development Process of Tadalafil: Tadalafil was initially discovered by scientists from Eli Lilly and Company in the United States by chance during the research of drugs for cardiovascular diseases. During the research process, they found that a compound had a unique mechanism of action in regulating vasodilation. Further research showed that this compound had a selective inhibitory effect on PDE5, which could increase the level of cGMP and promote the relaxation of the smooth muscles in the corpus cavernosum of the penis, thus improving erectile function. After a series of clinical trials and optimizations, Tadalafil was finally developed into a drug specifically used to treat erectile dysfunction and was approved for marketing in the United States in 2003.
Clinical Research and Application Expansion: A large number of clinical trials have confirmed the effectiveness and safety of Tadalafil in the treatment of erectile dysfunction. It can not only significantly improve the erectile function of patients and enhance the quality of sexual life but also has a long half-life, which can continuously exert its effect in the body for up to 36 hours, providing patients with more flexible choices for sexual life time. In addition, subsequent studies have also found that Tadalafil has certain potential in the treatment of other diseases, such as pulmonary arterial hypertension.
What is the mechanism of action of Tadalafil?
1. Mechanism of Action on Erectile Dysfunction
Action on PDE5 Enzyme: Tadalafil exerts its effect in the treatment of erectile dysfunction mainly by inhibiting phosphodiesterase 5 (PDE5). PDE5 can degrade cyclic guanosine monophosphate (cGMP), and cGMP plays a key role in the process of penile erection. When sexual stimulation occurs, nerve endings release nitric oxide (NO), and NO activates guanylate cyclase, promoting the conversion of guanosine triphosphate (GTP) into cGMP. cGMP relaxes the smooth muscles in the corpus cavernosum of the penis, allowing blood to flow into the corpus cavernosum, resulting in an erection. Tadalafil inhibits PDE5, reducing the degradation of cGMP and increasing the concentration of cGMP in local tissues, thus maintaining the relaxation state of the smooth muscles in the corpus cavernosum of the penis and promoting an erection[1].
Advantages of Long Half-life: The uniqueness of Tadalafil lies in its long half-life of 17.5 hours. This gives it a longer treatment window, and it can be administered on-demand or once daily to reach an effective steady-state plasma concentration. This characteristic provides patients with more flexibility in medication[1].
2. Mechanism of Action on Benign Prostatic Hyperplasia (BPH)
NO-cGMP-PDE5 Pathway: In men, lower urinary tract symptoms (LUTS) are mainly attributed to benign prostatic hyperplasia. The mechanism of action of Tadalafil in the treatment of BPH involves the nitric oxide (NO) - cyclic guanosine monophosphate (cGMP) - PDE5 pathway. PDE5 inhibitors such as Tadalafil can induce the relaxation of the smooth muscles in the bladder and prostate, which helps to improve the storage symptoms in animal models of overactive bladder and prostate. Preclinical and clinical data clearly show that Tadalafil is effective for patients with LUTS secondary to BPH, either as monotherapy or as an add-on therapy[2].
Advantages Compared with Other Drugs: Since LUTS-BPH and erectile dysfunction (ED) are common co-existing urinary system diseases in elderly men, Tadalafil has more advantages than α1-adrenergic receptors and should be the first choice. Unlike α1-adrenergic receptors and 5-α reductase inhibitors, Tadalafil is a safe and well-tolerated therapy that does not cause sexual dysfunction but can improve sexual function instead[2].
3. Mechanism of Action on Cerebral Small Vessel Disease
Improving Cerebral Blood Flow and Endothelial Function: Studies have shown that Tadalafil may improve cerebral blood flow and endothelial function in patients with cerebral small vessel disease by targeting the signaling molecule cyclic guanosine monophosphate (cGMP). In a randomized, double-blind, placebo-controlled, crossover pilot trial, patients with cerebral small vessel occlusive stroke were given a single dose of Tadalafil or placebo. The results showed that Tadalafil significantly increased the oxygen saturation in the cortical microvessels 180 minutes after administration, indicating that Tadalafil may improve cerebral perfusion in patients with cerebral small vessel disease, although the effect size is small. However, no significant difference was observed in transcranial Doppler measurements, and the evaluation of peripheral endothelial function also did not show obvious effects, and the results of endothelial biomarkers were conflicting. Further research is needed in the future to study the effects of long-term Tadalafil treatment on cerebrovascular reactivity and endothelial function to evaluate its general microvascular changes and effects in cerebral small vessel disease and stroke[3].
4. Mechanism of Action on Nephrotic Syndrome
Protecting Podocytes: In the nephrotic syndrome model, Tadalafil may inhibit the progression of renal injury by preventing podocyte damage and dysfunction of the glomerular filtration barrier. In rats with adriamycin (ADR)-induced nephrotic syndrome model, the Tadalafil treatment group was orally administered 10mg/kg of Tadalafil for 2 weeks. The results showed that compared with the ADR + placebo group, the ADR + Tadalafil group reduced proteinuria. Immunohistological and immunofluorescence assays showed that Tadalafil could prevent the decrease in the number of Wilms' tumor 1 (WT1)-positive cells caused by ADR. In human podocytes, Tadalafil increased the viability of ADR-treated cells, and this effect was eliminated by the cGMP-dependent protein kinase (PKG) inhibitor KT5823. In addition, Tadalafil could also prevent the increase in albumin permeability in ADR-treated cells [4].
5. Mechanism of Action on Diabetic Wound Healing
Increasing Nitric Oxide Activity: One of the characteristics of diabetes is the delayed and impaired wound healing, which may be due to the transient nitric oxide activity. Tadalafil is a potent phosphodiesterase 5 (PDE-5) inhibitor, which acts by preventing the interruption of nitric oxide-driven cyclic guanosine monophosphate (cGMP) in vascular smooth muscle cells and platelets. In a study, diabetic rats were randomly divided into two groups: one group was the diabetic full-thickness wound induction group, and the other group was the diabetic full-thickness wound oral Tadalafil (5mg/kg.b.w.) treatment group. The results showed that Tadalafil accelerated the wound healing process of diabetic rats, and compared with the untreated group, the treatment group significantly enhanced vascularization and epithelialization [5].
Source:PubMed[3]
What are the applications of Tadalafil?
1. Treatment of Erectile Dysfunction
Tadalafil is one of the important drugs for the treatment of erectile dysfunction (ED). With the development of phosphodiesterase 5 (PDE5) inhibitors, the treatment of ED has undergone a revolutionary change. Tadalafil (Cialis®; Eli Lilly and Company, Indianapolis, USA) is the latest and most versatile PDE5 inhibitor for the clinical treatment of ED. Its most unique feature is a long half-life of 17.5 hours, which provides a longer treatment window for on-demand administration and can produce an effective steady-state plasma concentration when administered once daily. Clinical trials have proven its safety and effectiveness in the treatment of ED of various severities and etiologies, including difficult-to-treat ED. Tadalafil inhibits PDE5, increases the concentration of cGMP in the smooth muscle cells of the corpus cavernosum of the penis, resulting in smooth muscle relaxation and increased blood supply to the penis, thus improving erectile function.
2. Treatment of Benign Prostatic Hyperplasia
In men, lower urinary tract symptoms (LUTS) are mainly attributed to benign prostatic hyperplasia (BPH). Treatment options aim to relax the smooth muscles of the prostate and/or reduce prostate enlargement. Tadalafil is a PDE5 inhibitor, and clinical data show that PDE5 inhibitors can induce the relaxation of the bladder and prostate, helping to improve the storage symptoms in animal models of overactive bladder and prostate. Tadalafil is effective as both monotherapy and add-on therapy for patients with LUTS secondary to BPH. In addition, since LUTS-BPH and erectile dysfunction (ED) are common urinary system diseases in elderly men, Tadalafil has more advantages than α1-adrenergic receptors and should be the first choice. Tadalafil is a safe and well-tolerated treatment method. Unlike α1-adrenergic receptors and 5-α reductase inhibitors, the latter two may lead to sexual dysfunction, while Tadalafil can improve sexual function.
3. Application in Wound Healing
Deep eutectic solvents (DESs) based on choline chloride (CC) were designed for the topical application of Tadalafil (TDF) to achieve wound healing. Formulating Tadalafil for topical use avoids systemic exposure. The prepared DES formulation of Tadalafil greatly increased the equilibrium solubility of Tadalafil and showed significant effects in an in vivo model of wound healing. In the incisional wound and burn wound models, compared with DES, the formulation F01 containing Tadalafil and lidocaine (LDC) showed a significant contraction of the incisional wound area within three weeks. In addition, the application of F01 in burn wounds resulted in less scar formation than any other group, including the positive control, making it a candidate for burn dressing formulations.
Wound healing in diabetic patients may be delayed and impaired due to transient nitric oxide activity. Tadalafil is a potent PDE-5 enzyme-specific inhibitor that can prevent the interruption of nitric oxide-driven cyclic guanosine monophosphate in vascular smooth muscle cells and platelets. Studies have shown that Tadalafil can accelerate the wound healing process of diabetic rats and significantly enhance angiogenesis and epithelialization in the treatment group, demonstrating that Tadalafil may have a practical role in stimulating wound healing in the diabetic state.
4. Potential Therapeutic Role in Cerebral Small Vessel Disease
New treatment methods for cerebral small vessel disease are crucial for reducing the risk of small vessel occlusive stroke and vascular cognitive impairment. A randomized, double-blind, placebo-controlled, crossover pilot trial studied the use of the PDE5 inhibitor Tadalafil targeting the signaling molecule cyclic guanosine monophosphate to explore whether it can improve cerebral blood flow and endothelial function in patients with cerebral small vessel disease and stroke. The results showed that Tadalafil significantly increased the oxygen saturation in the cortical microvessels 180 minutes after administration, indicating that Tadalafil may improve the vascular parameters of stroke patients with cerebral small vessel disease, although the effect size is small. Future research is needed on the effects of long-term Tadalafil treatment on cerebrovascular reactivity and endothelial function to evaluate its general microvascular changes and effects in cerebral small vessel disease and stroke.
5. Treatment of Preeclampsia
In an open-label, randomized clinical trial, the effectiveness and safety of Tadalafil in the treatment of hypertensive disorders of pregnancy (HDP) were evaluated. The results showed that no major adverse events related to Tadalafil occurred in the Tadalafil treatment group. There was a significant difference between the two groups in terms of maternal adverse events, especially headache (0% in the Tadalafil group and 43% in the conventional treatment group). Maternal headache was significantly reduced in the Tadalafil treatment group, and Tadalafil was safe for pregnant women with HDP, but it did not prolong the gestational period of pregnant women with HDP.
6. Research in Sports Medicine
The effects of acute intake of Tadalafil on plasma markers related to cell damage, redox homeostasis, and blood polyamine levels were studied in healthy subjects with a high level of cardiorespiratory function. The results showed that in subjects with a high fitness level, a single dose of Tadalafil led to a significant increase in muscle damage markers but did not affect the plasma antioxidant status.
In conclusion, Tadalafil has potential therapeutic applications in the fields of erectile dysfunction, benign prostatic hyperplasia, wound healing, cerebral small vessel disease, preeclampsia, and sports medicine.
About The Author
The above-mentioned materials are all researched, edited and compiled by Cocer Peptides.
Scientific Journal Author
Ölmestig J is a researcher associated with Herlev and Gentofte Hospital's Department of Neurology and Danish Research Centre for Magnetic Resonance. He is also a Ph.D. student at Amager and Hvidovre Hospital. His research interests are centered around Neurosciences & Neurology. He has made significant contributions to the understanding of neurological diseases and their treatment. He has investigated cerebral blood flow and endothelial function pre- and post tadalafil administration in patients with cerebral small vessel disease/lacunar stroke. His work has been published in reputable journals such as Cellular Signalling and Basic & Clinical Pharmacology & Toxicology. Ölmestig J is listed in the reference of citation [3].
