47 Synergy Between Sildenafil and Topically Delivered Nitric-oxide in Eliciting an Erectile Response in a Rat Model of Radical Prostatectomy
Abstract
ABSTRACT Introduction Sildenafil belongs to a group of phosphodiesterase-type-5-inhibitors (PDE5i) which represent the only class of FDA-approved oral treatments for erectile dysfunction (ED). However, because their mode of action is dependent on the production of nitric oxide (NO) from nerve endings, patients that undergo radical prostatectomy (RP), which results in cavernous nerve (CN) injury, are commonly refractory to these pharmacologic agents. Objective Our goal was to investigate the ability of topically applied microparticles capable of transdermal delivery of NO (NO-MP) to act synergistically with sildenafil in eliciting an erectile response in an animal model of RP. Methods As a model of RP, Sprague-Dawley rats underwent bi-lateral transection of the CN one-week prior to determining erectile response to treatment. Rats were treated by oral gavage of 0.05 and 0.005 mg sildenafil/kg, 30 minutes before being anesthetized for the determination of intracorporal pressure (ICP) and systemic blood pressure (BP). Baseline ICP and BP were recorded for 30 min, at which time 250 or 100 mg NO-MP (or control, blank-MP) were applied to the rat penile shaft. The ICP and systemic BP were used to determine the time to the first erectile response, duration of the erectile responses, the maximal and average ICP/BP responses and the number of spontaneous erections per hour. Results Although oral treatment with sildenafil by itself resulted in no observable erectile response, topical…
Read the paper
Related studies
- Drug repositioning: a brief overview
- Cyclic nucleotide phosphodiesterases in Drosophila melanogaster
- Time-resolved in silico modeling of fine-tuned cAMP signaling in platelets: feedback loops, titrated phosphorylations and pharmacological modulation
- Current View on Green Tea Catechins Formulations, Their Interactions with Selected Drugs, and Prospective Applications for Various Health Conditions
- In silico Structure-based Identification of Novel Acetylcholinesterase Inhibitors Against Alzheimer’s Disease
- Development and In Vitro Evaluation of Controlled Release Viagra® Containing Poloxamer-188 Using Gastroplus™ PBPK Modeling Software for In Vivo Predictions and Pharmacokinetic Assessments
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.