Sildenafil
(Synonyms: 西地那非; UK-92480) 目录号 : GC11369
西地那非，作为一种磷酸二酯酶 5 (PDE-5) 抑制剂，用于治疗肺动脉高压 (PAH)。
Cas No.:139755-83-2
Sample solution is provided at 25 µL, 10mM.
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| Cell experiment [1]: | |
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Cell lines |
Bovine aortic endothelial cells |
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Preparation Method |
Bovine aortic endothelial cells (BAECs), with or without pretreatment of sildenafil (5 μM at 5 minutes before radiation), were used to test endothelial dysfunction in response to external beam radiation at 10e15 Gy. Generation of reactive oxygen species (ROS) was studied. |
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Reaction Conditions |
5 μM at 5 minutes before radiation |
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Applications |
sildenafil (5 μM) added 5 minutes before 10 Gy radiation inhibited SDRT-induced apoptosis at 8 hours by 45% from 17.4% (SDRT alone) to 9.6% (SDRTþ sildenafil 5 μM). |
| Animal experiment [2]: | |
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Animal models |
Male, aged (16-18 months) Wistar rats |
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Preparation Method |
Male, aged (16-18 months) Wistar rats were subjected to MMI (800 ± 100, 70-100 μm cholesterol crystals injected into the internal carotid artery) and treated with or without Sildenafil (2 mg/kg, i.p) starting at 24 h after MMI daily for 28 days. |
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Dosage form |
2 mg/kg, i.p |
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Applications |
Sildenafil treatment in aged MMI rats significantly improves short term memory evaluated by the novel object recognition test and improves spatial learning and memory in the Morris water maze test compared to aged control MMI rats. |
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References: [1]. Wortel RC, et al. Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress. J Sex Med. 2019 Nov;16(11):1721-1733. [2]. Venkat P, et al. Sildenafil treatment of vascular dementia in aged rats. Neurochem Int. 2019 Jul;127:103-112. |
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Sildenafil, as a phosphodiesterase-5 (PDE-5) inhibitors, used for treatment of pulmonary arterial hypertension (PAH).[1] Sildenafil can also treat erectile dysfunction caused by the psychological stress of infertility treatments.[3]
In vitro, the IC50 of sildenafil for PDE5 was 5.22 nM.[4] In vitro experiment it indicated that treatment with 1 μmol/L sildenafil in pulmonary artery smooth muscle cells potentiated the phosphorylation of ERK1/ERK2, an increase in the percentage of cells in S phase and cell proliferation, compared with serotonin stimulation alone.[5] In vitro, the combination of sildenafil with cisplatin can improve cell toxicity and anticancer effect of cisplatin.[7]
In vivo efficacy test it shown that sildenafil dose-dependently (1 mg/kg every 12 hours for 14 days, p.o.) reduced basal tone and increased electrically-induced relaxation of dog lower oesophageal sphincter samples.[2] In vivo, treatment 10 mg/kg sildenafil after 72 h significantly increased the number of COX-2+ microglia/macrophages in the penumbra, but was remarkably decreased 8 days after ischemia.[6] SILD - EAE mice were treated with 25mg/kg Sildenafil (s.c.), the results shown that sildenafil inhibited nitrosative stress and augmented the levels of LC3, beclin-1, ATG5, p-CREB and BDNF and decreased mTOR levels, as well as augmented p-AMPK.[8] In vivo study it demonstrated that treatment with 40 mg/kg/day sildenafil can improve radiation-induced oral mucositis and decrease the apoptosis of mucosal cells via attenuation of inflammation and oxidative stress.[9]
References:
[1]Bhogal S, et al. Sildenafil for Pulmonary Arterial Hypertension. Am J Ther. 2019 Jul/Aug;26(4):e520-e526.
[2]Quintavalla F, et al. Sildenafil improves clinical signs and radiographic features in dogs with congenital idiopathic megaoesophagus: a randomised controlled trial. Vet Rec. 2017 Apr 22;180(16):404.
[3]Scherzer ND, et al. Sildenafil's impact on male infertility: what has changed in 20 years? Int J Impot Res. 2019 Mar;31(2):71-73.
[4]Wang Z, et al. The selectivity and potency of the new PDE5 inhibitor TPN729MA. J Sex Med. 2013 Nov;10(11):2790-7.
[5]Li BB, et al. Sildenafil potentiates the proliferative effect of porcine pulmonary artery smooth muscle cells induced by serotonin in vitro. Chin Med J (Engl). 2011 Sep;124(17):2733-40.
[6]Moretti R, et al. Sildenafil, a cyclic GMP phosphodiesterase inhibitor, induces microglial modulation after focal ischemia in the neonatal mouse brain. J Neuroinflammation. 2016 Apr 28;13(1):95.
[7]Hassanvand F, et al. Sildenafil enhances cisplatin-induced apoptosis in human breast adenocarcinoma cells. J Cancer Res Ther. 2020 Oct-Dec;16(6):1412-1418.
[8]Duarte-Silva E, et al. Sildenafil Alleviates Murine Experimental Autoimmune Encephalomyelitis by Triggering Autophagy in the Spinal Cord. Front Immunol. 2021 May 13;12:671511.
[9]Ala M, et al. Sildenafil improves radiation-induced oral mucositis by attenuating oxidative stress, NF-κB, ERK and JNK signalling pathways. J Cell Mol Med. 2022 Aug;26(16):4556-4565.
西地那非,作为一种磷酸二酯酶 5 (PDE-5) 抑制剂,用于治疗肺动脉高压 (PAH)。[1] 西地那非还可以治疗因心理压力引起的勃起功能障碍不孕症治疗。[3]
在体外,西地那非对PDE5的IC50为5.22 nM。[4] 体外实验表明,1 μmol/L西地那非处理肺动脉平滑肌细胞可增强ERK1的磷酸化/ERK2,与单用5-羟色胺刺激相比,S期细胞百分比和细胞增殖增加。[5] 在体外,西地那非与顺铂联合可提高细胞毒性和抗癌作用顺铂。[7]
体内功效测试表明,西地那非剂量依赖性（1 毫克/千克,每 12 小时一次,持续 14 天,口服）降低基础张力并增加狗食管下括约肌样本的电诱导松弛。[2] 在体内,72 小时后 10 mg/kg 西地那非处理显着增加半暗带中 COX-2+ 小胶质细胞/巨噬细胞的数量,但在缺血 8 天后显着减少。[6] SILD - 用 25mg/kg 西地那非 (s.c.) 治疗 EAE 小鼠,结果显示西地那非抑制亚硝化应激并增加 LC3、beclin-1、ATG5、p-CREB 和 BDNF 的水平,并降低 mTOR 水平,并增强p-AMPK.[8] 体内研究表明,用 40 mg/kg/天的西地那非治疗可以改善辐射引起的口腔粘膜炎,并通过减轻炎症和氧化应激来减少粘膜细胞的凋亡.[9]
| Cas No. | 139755-83-2 | SDF | |
| 别名 | 西地那非; UK-92480 | ||
| 化学名 | 5-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonylphenyl]-1-methyl-3-propyl-4H-pyrazolo[4,3-d]pyrimidin-7-one | ||
| Canonical SMILES | CCCC1=NN(C2=C1NC(=NC2=O)C3=C(C=CC(=C3)S(=O)(=O)N4CCN(CC4)C)OCC)C | ||
| 分子式 | C22H30N6O4S | 分子量 | 474.58 |
| 溶解度 | ≥ 46.3 mg/mL in DMSO with ultrasonic, ≥ 22.65 mg/mL in Water | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1071 mL | 10.5356 mL | 21.0713 mL |
| 5 mM | 0.4214 mL | 2.1071 mL | 4.2143 mL |
| 10 mM | 0.2107 mL | 1.0536 mL | 2.1071 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Sildenafil/Viagra in the treatment of premature ejaculation
The arrival of Pfizer's blue pill Sildenafil in 1998 brought a great relief both to patient and physician signalling the start of a great era of medical therapy in sexual medicine. Since then the sexual medicine experts have been prescribing sildenafil in erectile dysfunction with acceptable minor adverse events. But the use of sildenafil in premature ejaculation (PE) is still debated. 2018 being the 20th anniversary of sildenafil, we have compiled interesting facts about the role of sildenafil in PE from various original articles, systematic reviews, meta-analyses, economic brochures and sexual medicine committee guidelines. The major issues in most of these studies were the heterogeneity in the definition of PE and estimating the exact ejaculatory latency time. This perspective article highlights the positive role of sildenafil in the management of PE (even without ED) with acceptable adverse events. Now that we have a standardised definition of PE from International Society of Sexual Medicine (ISSM) and a psychogenic component in PE definition, more randomised placebo-controlled studies are required to further establish its role.
Sildenafil in ophthalmology: An update
Sildenafil citrate, a selective oral phosphodiesterase 5 inhibitor, is a widely used drug for erectile dysfunction that acts by elevating cGMP levels and causing smooth muscle relaxation. It also has 10% activity against PDE6, a key enzyme in phototransduction cascade in the retina. Recent ocular imaging developments have further revealed the influence of sildenafil on ocular hemodynamics, particularly choroidal perfusion. Choroidal thickness is increased, and choroidal perfusion is also enhanced by autoregulatory mechanisms that are further dependent on age and microvascular abnormalities. Studies demonstrating high intraocular pressure via a "parallel pathway" from increased choroidal volume and blood flow to the ciliary body have challenged previous concepts. Another new observation is the effect of sildenafil on bipolar cells and cyclic-nucleotide gated channels. We discuss potential deleterious effects (central serous chorioretinopathy, glaucoma, ischemic optic neuropathy, and risks to recessive carriers of retinitis pigmentosa), potential beneficial effects (ameliorate choroidal ischemia, prevent thickening of Bruch membrane, and promote recovery of the ellipsoid zone) in macular degeneration, as well as potential drug interactions of sildenafil.
Sildenafil for Pulmonary Arterial Hypertension
Pulmonary hypertension is a life-threatening illness with debilitating physical and emotional consequences. The progression of this devastating disease is characterized by a continuous increase in pulmonary vascular resistance, which results in elevated pulmonary artery pressure and leads to right heart failure. Treatment is focused on targeting the underlying complex etiology via the endothelin, prostacyclin, and nitric oxide (NO) pathways. Emergence of new treatments over the past 2 decades has led to improvement in the functional status and time to clinical worsening. Even with recent advances, outcomes remain suboptimal. Phosphodiesterase-5 (PDE-5) inhibitors, such as sildenafil, were approved for treatment of pulmonary arterial hypertension (PAH) by the Food and Drug Administration (FDA) in 2005, which holds promise in improving quality of life and therefore making this class of medications effective palliative therapy agents. In this review, we summarize the emergence of sildenafil as a treatment for PAH and its role as palliative therapy.
Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction: a systematic review and meta-analysis
Aims: Erectile dysfunction (ED) is a major care problem worldwide. Tadalafil and sildenafil are the two most common phosphodiesterase 5 inhibitors used to treat ED. This systematic review and meta-analysis were conducted to directly compare tadalafil with sildenafil for the treatment of ED.
Methods: We designed a strategy for searching the PubMed, Embase, EBSCO, Web of Science and Cochrane library databases; the reference lists of the retrieved studies were also investigated. A literature review was performed to identify all published randomized or non-randomized controlled trials that compared tadalafil with sildenafil for the treatment of ED and to assess the quality of the studies. Two investigators independently and blindly screened the studies for inclusion. The meta-analysis was performed using RevMan 5.0.
Results: A total of 16 trials that compared tadalafil with sildenafil for the treatment of ED were included in the meta-analysis. In the meta-analysis, tadalafil and sildenafil appeared to have similar efficacies and overall adverse event rates. However, compared with sildenafil, tadalafil significantly improved psychological outcomes. Furthermore, the patients and their partners preferred tadalafil over sildenafil, and no significant difference was found in the adherence and persistence rates between tadalafil and sildenafil. Additionally, the myalgia and back pain rates were higher and the flushing rate was lower with tadalafil than with sildenafil.
Conclusion: Tadalafil shares a similar efficacy and safety with sildenafil and significantly improves patients' sexual confidence. Furthermore, patients and their partners prefer tadalafil to sildenafil. Hence, tadalafil may be a better choice for ED treatment.
Sildenafil-associated hepatoxicity: a review of the literature
Sildenafil citrate (Viagra?) is a vasoactive agent available worldwide since 1998 for the treatment of male erectile dysfunction. It is a selective phosphodiesterase type 5-enzyme inhibitor able to potentiate the downstream effects of nitric oxide on smooth muscle relaxation and vasodilation through its effects on the cyclic guanosine monophosphate (c-GMP) pathway in the erectile tissue of the penis. When sildenafil is orally administered, it is rapidly absorbed with a maximum plasma concentration achieved within 1 h and has a terminal half-life of between 3 to 6 h. The drug is extensively and rapidly metabolized by the liver, primarily by the CYP3A4 enzyme. Although the drug is well tolerated, specific adverse events have been observed, like flushing, headaches, dyspepsia, and visual disturbances. Liver toxicity related to sildenafil consumption has been considered a very rare event. However, in the last decade, some cases of sildenafil-associated hepatotoxicity have been reported. Furthermore, some hepatic intoxications have been reported after the intake of "natural" or "herbal" aphrodisiac supplements sold through Internet, sex shops, social media, and by word-of-mouth found to contain sildenafil and other phosphodiesterase type 5 (PDE-5) inhibitors. Studies investigating a possible link between sildenafil use and liver damage are limited, and the underlying mechanism responsible for hepatotoxicity is still missing. Studies in animals evidence that the hematopoietic function of the liver may have severely been affected as a result of a probable toxic effect of sildenafil. Here, the studies reporting liver toxicity by sildenafil in humans and in animals are reported and discussed.