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111.
Sildenafil, tadalafil, vardenafil and verapamil induced concentration-dependent relaxation of the rabbit corpus cavernosum muscle precontracted with noradrenaline. The maximal relaxation (%) at 20 microM was 61.4 +/- 6.9, 32.4 +/- 5.4, 100.0 +/- 5.5 and 86.6 +/- 5.1 (n = 5 each) respectively. Pre-incubation of cavernosal muscle strips with N(omega)-nitro-L-arginine or guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) but not adenylate cyclase inhibitor, cis-N-[2-phenylcyclopentyl]-azacyclotridec-1-en-2-amine] (MDL12330A) culminated in only a 20-30% reduction in muscle relaxant action of the 3 phosphodiesterase inhibitors. This suggests that another mechanism of relaxation independent of nitric oxide-cGMP or cAMP pathway was involved. Higher concentrations of sildenafil (100 microM) and vardenafil (10 and 100 microM) produced non-competitive antagonism of noradrenaline-induced contraction characterized by reduced maximal effect. In contrast, tadalafil was devoid of significant effect on noradrenaline. On K(+)-depolarized tissues, sildenafil was as potent as vardenafil whereas tadalafil was the least effective in relaxing K(+)-induced tone. The maximal relaxation (% of K(+)-induced tone) at 20 microM sildenafil, tadalafil and vardenafil was respectively 84.1 +/- 6.5, 9.0 +/- 19.9, and 88.9 +/- 6.2 (n = 5 each). In addition, verapamil, sildenafil and vardenafil were more efficacious than tadalafil in reversing tonic contractions by Ca(2+) channel activator, 1,4,dihydro-2,6-dimethyl-5-nitro-4-[2(triflouromethyl)phenyl]pyridine-3-carboxylic acid methyl ester (BAY K-8644). These results indicate that vardenafil and sildenafil possess direct muscle relaxant potential possibly via inhibiting Ca(2+) influx through both receptor-operated and voltage-dependent Ca(2+) channels whereas tadalafil appears capable of inhibiting receptor-operated transmembrane Ca(2+) entry only. 相似文献
112.
Yoko Ichikawa-Kaji Fujio Ishizawa Rei Nishiyama Hajime Tachikawa Nozomi Uemura Yuka Moriuchi Yi-Yang Hsiao Takako Moriyasu Toshinari Suzuki Yoichiro Takahashi Akiko Inomata 《Drug testing and analysis》2023,15(3):345-360
Sexual enhancement products adulterated with phosphodiesterase 5 inhibitors (PDE-5i) pose a serious public health concern. Tadalafil and its analogues (Tds) are PDE-5i frequently detected as adulterants. In this study, a Td detector tube for the rapid detection of Tds was developed based on the color change reaction between sulfuric acid and Tds. The specificity of this test method was evaluated using 13 Tds, all of which elicited positive results. Additionally, 30 commonly found adulterants in dietary supplements, 11 active pharmaceutical ingredients of psychotropic drugs and 18 food ingredients were tested and obtained no false-positive results, except levomepromazine. The test tube accurately detected the presence or absence of Tds in 54 commercially available products. The visual detection limit was 2–50 and 5–20 μg/ml for Tds and tadalafil-spiked samples with matrix, respectively. The applicability of the developed detector tube to a semiquantitative test using digital image analyses were investigated using red, green, and blue color values. The results of the recovery test suggested that the tube test was affected by the dark-colored matrix. The results of semiquantitative analyses of tadalafil for five marketed products were consistent with the liquid chromatographic quantification results, except for the blue value. The detector tube developed in this study can facilitate with the rapid screening of Tds in adulterated sexual enhancement products. 相似文献
113.
目的探讨单用他达拉非5mg/日以及联用硫辛酸治疗糖尿病性ED的临床疗效。方法选择2017年1月至2018年12月就诊我科的糖尿病性ED患者181例,经第一阶段他达拉非5mg/日治疗12周后,仍诉勃起功能障碍及部分合并射精功能障碍的43例患者纳入最终研究统计并接受第二阶段治疗;第二阶段采用他达拉非5mg/日联合硫辛酸治疗12周。最终纳入研究统计患者在治疗前及第一、第二阶段治疗后均使用IIEF-5、Rigiscan及男性射精功能评分量表分别评估勃起满意度、勃起功能、射精功能等并记录。通过三次结果分析单用他达拉非5mg/日及联用硫辛酸治疗糖尿病性勃起功能障碍及合并射精功能障碍的疗效。结果他达拉非5mg/日联合硫辛酸治疗较单用他达拉非5mg/日及治疗前均显著提高患者IIEF-5分值,差异有统计学意义(P<0.05);单用他达拉非5mg/日及联合硫辛酸治疗较治疗前Rigiscan检测参数均有提高,差异有统计学意义(P<0.05),他达拉非5mg/日联合硫辛酸相比单用他达拉非5mg/日除阴茎头部胀大活力单位(Tumescence Activity Units TAU)差异无统计学意义(P>0.05),其余参数差异均有统计学意义(P<0.05)。糖尿病性ED伴Ej D患者单用他达拉非5mg/日治疗后男性射精功能评分较治疗前差异无统计学意义(P>0.05);联用硫辛酸治疗后部分射精功能评分项改善,较治疗前及单用他达拉非5mg/日治疗差异有统计学意义(P<0.05)。结论单用他达拉非5mg/日或联用硫辛酸均可改善糖尿病性ED患者的勃起功能,联用硫辛酸可改善部分射精功能。 相似文献
114.
目的:探讨阴茎负压吸引(VED)联合小剂量他达拉非口服治疗糖尿病性勃起功能障碍(EDDM)的有效性和安全性。方法:选取70例DED患者,随机将其分为治疗组和对照组各35例,对照组给予他达拉非片5mg口服,每晚1次,8周为1疗程。治疗组在对照组治疗的基础上加用真空阴茎负压吸引治疗8周;比较治疗前、治疗结束时的IIEF-5评分、性生活日志(Sexual Encounter Profile,SEP)中的SEP-Q2(successful penetration)、SEP-Q3(successful completion of intercourse)变化。结果:两组患者治疗后IIEF-5评分、插入成功率及性交成功率均较治疗前提高(P<0.05),试验组IIEF-5评分治疗前、治疗结束分别为(11.61±2.89)、(20.85±2.18),对照组IIEF-5评分治疗前、治疗结束时分别为(11.38±3.15)、(17.40±2.64),治疗后插入成功率(SEP-Q2)两组分别为62.9%、91.4%,性交成功率(SEP-Q3)两组分别为60%、91.4%,联合治疗组相比较效果更明显(P<0.05),两组均未出现严重不良反应。结论:真空负压吸引联合小剂量他达拉非口服治疗糖尿病性ED疗效显著,值得临床应用。 相似文献
115.
116.
Sang-Bin Baek Geonho Bahn Su-Jin Moon Jiah Lee Khae-Hawn Kim Il-Gyu Ko Sung-Eun Kim Yun-Hee Sung Bo-Kyun Kim Tae-Soo Kim Chang-Ju Kim Mal-Soon Shin 《Neuroscience letters》2011
Early adverse experiences resulting from maternal separation may lead to neuronal cell death and eventually cause memory impairment. Maternal separation has been used to create a valid animal model of early life stress and a depression-like syndrome. The phosphodiesterase (PDE)-5 inhibitor, tadalafil (Cialis), is a widely prescribed agent for the treatment of erectile dysfunction. In this study, we investigated the effects of tadalafil on apoptosis and cell proliferation in the hippocampal dentate gyrus of rat pups following maternal separation. Specifically, the immobility time in the forced swim test was increased in the maternal-separated rat pups, and tadalafil treatment decreased the immobility time. The rat pups in the maternal separation group had deceased memory function compared to the rat pups in the maternal care group, and tadalafil treatment increased memory function of the rat pups in the maternal separation group. Apoptotic cell death in the hippocampal dentate gyrus was significantly increased in the maternal-separated rat pups, and tadalafil treatment suppressed maternal separation-induced apoptosis. In contrast, cell proliferation in the dentate gyrus was significantly decreased in the maternal-separated rat pups, and taldalafil treatment increased cell proliferation. The present results suggest that tadalafil improves depressive symptoms and alleviates memory impairment by suppressing apoptotic neuronal cell death and enhancing cell proliferation in maternal-separated rat pups. 相似文献
117.
目的:观察性行为与心理疗法(停-动-停训练及默算性交抽动的次数)配合他达拉非+氟西汀治疗非器质性早泄的临床疗效.方法:352例确诊为非器质性早泄患者中,年龄22~41岁,平均28.30岁;病程6个月~8年,平均2.6年.随机分为治疗组102例(性交前2~4h口服他达拉非20mg+氟西汀20mg配合性行为与心理疗法)和对... 相似文献