The role played by spinal adrenergic and cholinergic receptors in the antinociceptive effects of intrathecal sildenafil in formalin-induced nociception was examined. Intrathecal catheters were inserted into the subarachnoid space of male Sprague-Dawley rats, and nociception was assessed using the formalin test, consisting of a subcutaneous injection of 50 μL of 5% formalin solution into the hind paw. We examined the effects of an alpha 1 adrenergic receptor antagonist (prazosin), an alpha 2 adrenergic receptor antagonist (yohimbine), a muscarinic acetylcholine receptor antagonist (atropine), and a nicotinic acetylcholine receptor antagonist (mecamylamine) on sildenafil-induced antinociception. Intrathecal sildenafil (3, 10, and 30 μg) suppressed, in a dose-dependent manner, formalin-induced flinching during phases 1 and 2 of the test. Intrathecal sildenafil (30 μg) could not show any effects against intrathecal prazosin (3 μg), yohimbine (10 μg), atropine (10 μg), and mecamylamine (10 μg) pretreatment during both phases of the formalin test. These results suggest that intrathecal sildenafil effectively attenuated the pain evoked by formalin injection. Additionally, spinal alpha 1, alpha 2, muscarinic and nicotinic receptors might play a role in sildenafil-induced antinociception. 相似文献
Successful embryo implantation depends on a well-functioning endometrium and high-grade quality embryos. An increasing body of evidence suggests that sildenafil citrate plays an important role in endometrial receptivity and implantation. However, few studies have investigated the effects of oral sildenafil citrate on the clinical outcomes of patients with recurrent implantation failure (RIF). In the present study, we aimed to determine the impact of sildenafil citrate on improving the endometrial blood flow and pregnancy rate in RIF patients. A total of 346 frozen-thawed transfer cycles from 305 RIF patients undergoing IVF at the Center for Reproductive Medicine of Peking University Third Hospital from June 2013 to December 2017 were enrolled. Oral sildenafil citrate was given to the patients, and the related effects on endometrial blood flow, endometrial thickness, and clinical outcomes were investigated. In the 346 transferred cases, the proportion of three groups (A: undetectable blood flow; B: sub-endometrial blood flow; C: endometrial and sub-endometrial blood flow) before and after oral administration of sildenafil citrate was as follows: group A: 36.7% ( n = 127) vs. 7.5% ( n = 26); group B: 42.8% ( n = 148) vs. 24.0% ( n = 83); group C: 20.5% ( n = 71) vs. 68.5% ( n = 237). Moreover, the endometrial blood flow in 137 FET cycles was improved (61.8%). Besides, the implantation rate was 19.47% (132/678), and the clinical pregnancy rate reached 32.66% (113/346), while the endometrial blood flow of the pregnancy group was better compared with the non-pregnancy group. This study explored the improving effects of sildenafil citrate on the endometrial receptivity and clinical outcomes of RIF patients, confirming the crucial role of good endometrial blood flow in a successful pregnancy. Meanwhile, the low incidence of adverse events also supported the security and feasibility of sildenafil citrate in the clinical therapy of RIF patients. 相似文献
Summary. The phosphodiesterase (PDE) 5 inhibitor sildenafil has been shown to display psychotropic actions in humans and animals, and
has been used for the treatment of antidepressant-associated erectile dysfunction. However, its effects on the neurobiology
of depression are unknown. Nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) inhibition is anti-depressant in animals,
and increasing cGMP with sildenafil is anxiogenic in rodents. Substantial cholinergic-nitrergic interaction exists in the
brain, while sildenafil shows modulatory actions on cholinergic transmission. Depression is also associated with increased
cholinergic drive. Here we report that sildenafil increases muscarinic acetylcholine receptor (mAChR) signaling in human neuroblastoma
cells. We also show that fluoxetine (20 mg/kg/day × 7 days), as well as a combination of sildenafil (10 mg/kg/day × 7 days)
plus the antimuscarinic atropine (1 mg/kg/day × 7 days) demonstrates significant, comparable antidepressant-like effects in
the rat forced swim test (FST) and also reduces cortical β-adrenergic receptor (β-AR) density, while sildenafil or atropine
alone did not. Importantly, sildenafil did not modify fluoxetine’s response. Sildenafil thus demonstrates antidepressant-like
effects but only after central muscarinic receptor blockade, providing evidence for cholinergic-nitrergic interactions in
the neurobiology of depression.
Correspondence: Christiaan B. Brink, Division of Pharmacology, North-West University (PUK), Internal Box 16, Potchefstroom
2520, South Africa 相似文献
Purpose: To determine the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy (3D-CRT) for prostate cancer.
Methods and Materials: 406 patients with complaints of erectile dysfunction and who completed radiation at least 6 months before the study were approached by mail. 3D-CRT had been delivered (mean dose 68 Gy). Sixty patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received during 2 weeks 50 mg of sildenafil or placebo; at Week 2 the dose was increased to 100 mg in case of unsatisfactory erectile response. At Week 6, patients crossed over to the alternative treatment. Data were collected using the International Index of Erectile Function (IIEF) questionnaire, and side effects were recorded.
Results: Mean age was 68 years. All patients completed the study. For most questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with sildenafil, but not with placebo. Ninety percent of the patients needed a dose adjustment to 100 mg sildenafil. Side effects were mild or moderate.
Conclusion: Sildenafil is well tolerated and effective in improving erectile function of patients with ED after 3D-CRT for prostate cancer. 相似文献