Effects of omapatrilat on blood pressure and the progression of renal failure in an experimental model of type ii diabetes mellitus

García-Robles, Reggie; Villabla, F.; González-Albarrán, O.; Gómez, Oscar; Rábano, Alberto; Ruilope, Luis; Hurtado, Abdías; Sancho, José

doi:10.1016/s0895-7061(00)00385-x

Cited by 6 publications

(3 citation statements)

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“…98 When compared with captopril in a rodent model of diabetic nephropathy, omapatrilat provided greater protection against renal end-organ damage. 99 In a model of chronic renal failure, Taal et al 100 administered omapatrilat or enalapril maleate to rats, beginning 4 weeks after a fourfifths nephrectomy, after the onset of hypertension and proteinuria. Although both agents normalized BP, omapatrilat produced substantially greater reductions in the long-term evolution of proteinuria and glomerulosclerosis.…”

Section: Renal Diseasementioning

confidence: 99%

Role of the Natriuretic Peptide System in Cardiorenal Protection

McFarlane

Winer²,

Sowers³

2003

Arch Intern Med

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Significant progress has been made in the understanding of the neurohormonal factors that contribute to the progression of chronic renal and cardiac failure and the development of target-organ damage in patients with hypertension and diabetes. We herein review some of these advances, including a new therapeutic strategy for potentially enhancing cardiorenal protection in patients with these disorders.

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Section: Renal Diseasementioning

confidence: 99%

Role of the Natriuretic Peptide System in Cardiorenal Protection

McFarlane

Winer²,

Sowers³

2003

Arch Intern Med

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“…However, in order to fully develop ligands exhibiting dual or polypharmacology, ensuring the clinical efficacy of both, or multiple targets in combination is necessary, which may be more costly and time-consuming. Failure using DMLs was seen with the antihypertensive drug omapatrilat [97] which was designed to inhibit both neutral endopeptidase 24.11 (NEP) and angiotensin converting enzyme (ACE) [98] as a putative solution to treating high blood pressure and heart failure [99]. Both enzymes are involved in the breakdown of bradykinin [100].…”

Section: Multitargeted Single Agentsmentioning

confidence: 99%

Personalized Medicine: the Impact on Chemistry

Watkins

Marsh

Taylor

et al. 2010

Therapeutic Delivery

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An effective strategy for personalized medicine requires a major conceptual change in the development and application of therapeutics. In this article, we argue that further advances in this field should be made with reference to another conceptual shift, that of network pharmacology. We examine the intersection of personalized medicine and network pharmacology to identify strategies for the development of personalized therapies that are fully informed by network pharmacology concepts. This provides a framework for discussion of the impact personalized medicine will have on chemistry in terms of drug discovery, formulation and delivery, the adaptations and changes in ideology required and the contribution chemistry is already making. New ways of conceptualising chemistry's relationship with medicine will lead to new approaches to drug discovery and hold the promise of delivering safer and more effective therapies.

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“…In experimental diabetes, vasopeptidase inhibition reduced albuminuria and lead to improvement of renal function [20]. In obese Zucker rats with unilateral nephrectomy, vasopeptidase inhibition revealed greater renal protection in terms of reduced proteinuria compared with ACE inhibition [52]. These favorable renal effects could be confirmed in Wistar rats after subtotal nephrectomy [53,54].…”

Section: Vasopeptidase Inhibitors and The Kidneymentioning

confidence: 99%

Vasopeptidase inhibition: Effective blood pressure control for vascular protection

Quaschning

Ruschitzka²,

Lüscher³

2002

Current Science Inc

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Angiotensin converting enzyme (ACE) inhibition is a well-established principle in the treatment of hypertension, and numerous large scale clinical studies have clearly demonstrated the beneficial effects of inhibiting the renin-angiotensin-aldosterone system (RAS) in hypertension. The clinical success of ACE inhibitors encouraged attempts to inhibit other key enzymes in the regulation of vascular tone, such as the neutral endopeptidase (NEP). Similar to ACE, NEP is an endothelial cell surface metalloproteinase, which is involved in the degradation of several regulatory peptides including the natriuretic peptides, and augments vasodilatation and natriuresis through increased levels of atrial natriuretic peptide. By inhibiting the RAS and potentiating the natriuretic peptide system at the same time, combined NEP/ACE inhibitors, the so-called "vasopeptidase inhibitors," reduce vasoconstriction and enhance vasodilatation, and in turn decrease peripheral vascular resistance and blood pressure. Within the vessel wall this may lead to a reduction of vasoconstrictor and proliferative mediators such as angiotensin II and endothelin-1, and may increase local levels of bradykinin as well as natriuretic peptides. Based on these considerations, numerous preclinical studies with vasopeptidase inhibitors have been performed and reveal promising results in experimental hypertension. Correspondingly, large-scale clinical studies in patients with hypertension are on the way, to transfer the principle of vasopeptidase inhibition from bench to bedside.

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Effects of omapatrilat on blood pressure and the progression of renal failure in an experimental model of type ii diabetes mellitus

Cited by 6 publications

References 0 publications

Role of the Natriuretic Peptide System in Cardiorenal Protection

Role of the Natriuretic Peptide System in Cardiorenal Protection

Personalized Medicine: the Impact on Chemistry

Vasopeptidase inhibition: Effective blood pressure control for vascular protection

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