Sildenafil

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]