Frontiers in Cardiovascular Drug Discovery: Volume 6 E-Book
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- Herausgeber: Bentham Science Publishers
- Kategorie: Fachliteratur
- Sprache: Englisch
Frontiers in Cardiovascular Drug Discovery is a book series devoted to publishing the latest advances in cardiovascular drug design and discovery. Each volume brings reviews on the biochemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, recent important patents, and structure-activity relationships of molecules used in cardiovascular therapy. The book series should prove to be of great interest to all medicinal chemists and pharmaceutical scientists involved in preclinical and clinical research in cardiology.
Volume 6 covers the following topics:
- Cardiovascular effects of ranolazine and the scope for translational research: a current review of literature
- Rho/Rho kinase signaling pathway and disease:
- Hibernation or transformation? Challenges in cardiovascular drug development
- New approaches in P2Y12 receptor blocker drugs use
- Pathophysiological links between diabetes and cardiovascular diseases: at the biochemical and molecular levels
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Seitenzahl: 469
Veröffentlichungsjahr: 2003
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PREFACE
Despite major developments in the early diagnosis and understanding of underlying molecular mechanisms, cardiovascular diseases (CVDs) remain the leading cause of death (31% death globally), followed by cancers. The risk of developing CVDs is highest among all non-communicable diseases. It has increased multi-fold with the increase in prevalence of metabolic disorders, including obesity. CVDs affect people of all regions and all ages, and there are many socio-demographic risk factors. Despite major basic research in this area, translating laboratory discoveries into therapeutic interventions remains a major challenge, and only a handful of drugs have reached to clinical application. Thus drug development against cardiovascular diseases has many unique challenges which large pharmaceutical companies are often not willing to address. The 6th volume of the book series entitled, “Frontiers in Cardiovascular Drug Discovery” is a compilation of five reviews on diverse topics, including translational research towards improved drugs, various molecular pathways and biomarkers to be targeted for the drug discovery as well as challenges in cardiovascular drug development.
The review by Pratiti et al is focused on the piperazine-based drug ranolazine for the treatment of various cardiovascular diseases. Ranolazine was initially developed as an oral antianginal medicine, and later identified as a versatile cardiovascular drug against various indications. The authors have provided a detailed account of translational research work carried out on ranolazine for a whole range of other CVDs. In the second chapter Zhang et al have emphasized the importance of Rho/Rho kinase (ROCK) as an important drug target. Rho/Rho kinase is related to cardiovascular conditions such as coronary atherosclerosis, hypertension, and heart failure. Selective inhibitors of ROCK can treat many CVDs. This article presents the relationship between various CVDs and Rho/Rho kinase, and thus validates this as a legitimate drug target. Numerous examples of ROCK inhibitors with potential as drugs are also presented.
The review article of G. Mercanoglu and F. Mecanoglu provides a comprehensive account of major challenges and bottlenecks in CVD drug development, that have resulted in a huge vacuum in this drug pipeline. The authors have commented on reasons of a gradual shift of CVD drug development from large pharmaceutical companies to medium pharma industries, small biotech firms and research and development institutions. A field which was historically considered as a “profitable” area of therapeutic research and development now needs support from World Health Organizations and other NGOs. With this background, the authors have provided some logical solutions to overcome the existing problems. Platelet P2Y12 receptor (P2Y12R) for adenosine 5'diphosphate (ADP) plays a central role in platelet function, hemostasis, and thrombosis. Akaydin et al have discussed various approaches to inhibit P2Y12 receptors for the prevention of platelet aggregation and thrombosis. These inhibitors can also prevent and treat ischemic complications in patients with unstable angina, myocardial infarction and coronary intervention. Various classes of P2Y12 inhibiting drugs and their clinical outcomes are discussed. Kabir et al have contributed a comprehensive review on the nexus of diabetes and cardiovascular diseases such as atherosclerosis, hypertension and myocardial infarction. CVD is the most prevalent cause of mortality in the diabetic population. The authors have also provided a detailed account of the mechanisms of the onset of these diseases. Studies of the molecular mechanisms involved in the progression of CVDs in diabetes as well as biomarker identification can not only contribute to the early diagnosis and prevention of the disease, but it can also help in the novel target identification for anti-diabetic and anti-CVD drug development.
I would like to express our gratitude to all the authors for their scholarly contributions, and for the timely submissions of their reviews. The production team of Bentham Science Publishers also deserves our appreciation for the job very well done. Among them Ms. Mariam Mehdi (Assistant Manager Publications), and Mr. Mahmood Alam (Director Publications) have played a key role in the timely completion of the volume in hand. We sincerely hope that the efforts of authors and production team will help readers in a better understanding of the recent important developments in this key area of therapeutic intervention.
List of Contributors
Cardiovascular Effects of Ranolazine and the Scope for Translational Research: A Current Review of Literature
Rebecca Pratiti1,*,Parul Sud1,Mohammad Yousef1,Ankush Moza2Abstract
Ranolazine is approved for symptomatic stable angina patients on standard antianginal therapy. It inhibits myocardial late sodium current (INa) and partially inhibits fatty acid oxidation. INa is increased in the pathological conditions of ischemia and heart failure. Ranolazine changes myocardial fatty acid beta-oxidation to glucose oxidation, making the heart more oxygen efficient in ischemia. Thus, ranolazine improves myocardial desynchrony, mechanical dysfunction, diastolic depolarization, and action potential duration during ischemia. The book chapter focuses on salient features of ranolazine with emphasis on its indication in cardiovascular medicine, the knowledge gap in its translational research, and future scope. One of the important findings of the review is that ranolazine is a versatile cardiovascular medicine with effects on angina, heart failure, arrhythmia, and cardiomyopathy. Most animal studies of ranolazine had a correlation with human trials. Ranolazine, with its current cost and side effects profile, could be a second-line medication for angina, heart failure, and arrhythmia, specifically for patients having intolerance or side effects to first-line medications. Ranolazine as a pain modulator in angina, myotonia, and claudication needs to be further studied. Ranolazine may improve cardioversion rates in cardioversion and treatment-resistant patients with paroxysmal atrial fibrillation. Ranolazine is an option for preventing recurring shocks in patients with defibrillators who have recurrent ventricular tachycardias. Diabetes, hibernating myocardium and reperfusion injury are major modulators of ranolazine’s treatment outcomes. Subsequently, better outcomes are seen in the presence of these pathologies. Ranolazine has similar efficacy as most oral hypoglycemics, and long-term studies are needed to evaluate its outcomes in diabetics with angina.
