scholarly journals Phosphodiesterase Type 5 Inhibitors Greatly Affect Physicochemical Properties of Model Lipid Membranes

Membranes ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 893
Author(s):  
Anastasiia A. Zakharova ◽  
Svetlana S. Efimova ◽  
Olga S. Ostroumova
Keyword(s):  
Special Interest ◽  
Lipid Membranes ◽  
Pharmacological Action ◽  
Membrane Curvature ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Membrane Dipole Potential ◽  
Model Lipid Membranes ◽  
Potential Benefits ◽  
Phosphodiesterase Type

Although phosphodiesterase type 5 inhibitors are widely used and well-studied drugs, the potential benefits of their application in the treatment of various diseases and new drug delivery systems, including liposome forms, are still being discussed. In this regard, the role of the lipid matrix of cell membranes in the pharmacological action of the inhibitors is of special interest. It was shown that sildenafil, vardenafil, and tadalafil caused a significant decrease in the boundary potential of model membranes composed of palmitoyloleoylphosphatidylcholine or its mixture with cholesterol, by 70–80 mV. The reduction in the membrane dipole potential induced by inhibitors led to a 20–25% increase in the conductance of cation-selective pores formed by the antimicrobial peptide gramicidin A. The addition of sildenafil or vardenafil also led to a significant decrease in the temperature of the main phase transition of dipalmytoylphosphatidylcholine, by about 1.5 °C, while tadalafil did not change the melting temperature. Sildenafil, vardenafil, and tadalafil enhanced the pore-forming activity of the antifungal polyene antibiotic nystatin by 11, 13, and 2 times, respectively. This fact might indicate the induction of membrane curvature stress by the inhibitors. The data obtained might be of special interest for the development of lipid-mediated forms of drugs.

scholarly journals Non-classical effects of sildenafil in clinical medicine: an interdisciplinary approach

2019 ◽  
pp. 192-202
Author(s):  
I. A. Tyuzikov ◽  
A. V. Smirnov ◽  
L. V. Smirnova ◽  
I. V. Lesnikova
Keyword(s):  
Erectile Dysfunction ◽  
Clinical Medicine ◽  
Experimental Studies ◽  
Interdisciplinary Approach ◽  
Pharmacological Action ◽  
Modern Medicine ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Medical Specialties ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Phosphodiesterase Type

Based on the results of modern clinical and experimental studies, the review article discusses issues of pharmacotherapeutic feasibility, pathogenetic validity and safety of the first and most studied phosphodiesterase type 5 inhibitor – sildenafil – in general clinical practice according to «non-classical» (non-erectogenic) indications in the framework of an interdisciplinary approach modern medicine. As it is known, at present, phosphodiesterase type 5 inhibitors are both the «first line» therapy for treating erectile dysfunction (as monotherapy), as well as an effective option for monotherapy or combined pharmacotherapy of lower urinary tract symptoms on the background of benign prostatic hyperplasia in men with erectile dysfunction. However, given the universality and fundamentality of the mechanisms of their pharmacological action (first of all, the effect on the metabolism of one of the key vasomodulators of the vascular bed, nitric oxide NO), the list of potential and promising indications for prescribing these drugs is constantly expanding due to the presence of various «non-classical» (non-erectogenic) effects, which makes them very attractive for wider application not only in urological practice, but also in other medical specialties. The article describes in more detail and purposefully the accumulated to date scientific and practical data on the effectiveness of the use and potential mechanisms of action of sildenafil in cardiology, endocrinology, neurology, nephrology, obstetrics and gynecology, andrological reproductology and oncology, and also presents the results of studies confirming its safety in the treatment of relevant specialized diseases.

scholarly journals Developing Martini Coarse-Grained Nitrogen Gas Model for Lipid Nanobubble Simulations

2021 ◽  
Author(s):  
Fujia Tian ◽  
Xubo Lin
Keyword(s):  
Cell Membrane ◽  
Lipid Membranes ◽  
Molecular Mechanisms ◽  
Membrane Curvature ◽  
Dynamics Simulation ◽  
Coarse Grained ◽  
Atomistic Simulations ◽  
Nitrogen Gas ◽  
Hydrophobic Region

<p>By integrating the advantages of lipids’ biocompatibility and nanobubbles’ potent physicochemical properties, lipid nanobubbles show a great potential in ultrasound molecular imaging and biocompatible drug/gene delivery. However, under the interactions of the ultrasound, lipid nanobubbles may fuse with the cell membrane, changing the local membrane component and re-distributing encapsulated gas molecules into the hydrophobic region of the cell membrane, which may greatly affect the dynamics of certain membrane proteins and thus functions of cells. Although molecular dynamics simulation provides a useful computational tool to reveal the related molecular mechanisms, the lack of coarse-grained gas model greatly restricts this purpose. In the current work, we developed a Martini-compatible coarse-grained gas model based on the results of previous experiments and atomistic simulations, which could be used for lipid nanobubble simulations with complicated lipid components. By comparing the results of well-designed lipid nanobubble, lipid bi-monolayer and lipid bilayer simulations, we further revealed the role of membrane curvature and interleaflet coupling in the liquid-liquid phase separation of lipid membranes. It is worth mention that our developed coarse-grained nitrogen gas model can also be used for other gas-water interface systems such as pulmonary surfactant, which may overcome the possible artefacts arising from the usage of vacuum for gas phase. </p>

scholarly journals Phosphodiesterase Type 5 Inhibitors For The Treatment of Erectile Dysfunction: Role Of The Patient Preference

2009 ◽  
Vol 19 (3) ◽  
pp. 100-105
Author(s):  
Ömer Demir ◽  
Ali Feyzullah Şahin ◽  
Oktay Üçer ◽  
Ertan Can ◽  
Bilali Gümüş ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Patient Preference ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Phosphodiesterase Type
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