Pharmacological modulation of the natriuretic peptide system

Venugopal, Joshi

doi:10.1517/13543776.13.9.1389

Cited by 10 publications

(8 citation statements)

References 122 publications

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“…Another NEP inhibitor drug, omapatrilat, developed by Bristol-Myers Squibb also initially showed promise as an antihypertensive agent. However, safety concerns led to it being withdrawn from clinical trials in 2003 (47). Because the opiorphin peptides also act as NEP inhibitors, their mechanism of action could overlap with the synthetic NEP inhibitors and they could be applied to the treatment of similar types of medical conditions.…”

Section: Discussionmentioning

confidence: 99%

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Reversal of diabetic vasculopathy in a rat model of type 1 diabetes by opiorphin-related peptides

Calenda

Tong²,

Kanika³

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Diabetes results in a myriad of vascular complications, often referred to as diabetic vasculopathy, which encompasses both microvascular [erectile dysfunction (ED), retinopathy, neuropathy, and nephropathy] and macrovascular complications (hypertension, coronary heart disease, and myocardial infarction). In diabetic animals and patients with ED, there is decreased opiorphin or opiorphin-related gene expression in corporal tissue. Both opiorphin and the rat homologous peptide sialorphin are found circulating in the plasma. In the present study, we investigated if diabetes induced changes in plasma sialorphin levels and if changes in these levels could modulate the biochemistry and physiology of vascular smooth muscle. We show that circulating sialorphin levels are reduced in a rat model of type I diabetes. Intracorporal injection of plasmids expressing sialorphin into diabetic rats restores sialorphin levels to those seen in the blood of nondiabetic animals and results in both improved erectile function and blood pressure. Sialorphin modulated the ability of C-type natriuretic peptide to relax both corporal and aortic smooth muscle strips and of bradykinin to regulate intracellular calcium levels in both corporal and aortic smooth muscle cells. We have previously shown that expression of genes encoding opiorphins is increased when erectile function is improved. Our findings thus suggest that by affecting circulating levels of opiorphin-related peptides, proper erectile function is not only an indicator but also a modulator of overall vascular health of a man.

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Section: Discussionmentioning

confidence: 99%

“…Another NEP inhibitor drug, omapatrilat, also initially showed promise as an antihypertensive agent. However, because of safety concerns it was withdrawn from clinical trials in 2003 (47).…”

mentioning

confidence: 99%

Reversal of diabetic vasculopathy in a rat model of type 1 diabetes by opiorphin-related peptides

Calenda

Tong²,

Kanika³

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…Omapatrilat inhibits both NEP and ACE and was found to be more effective than ACE inhibitors alone. However, it has not received FDA approval due to angioedema safety concerns [82] . Other dual NEP/ACE inhibitors are BMS‐182657, MDL‐100173 and S21402 (RB105) {N‐[2S,3R‐(2‐mercaptomethyl‐1‐oxo‐3‐phenylbutyl)‐ l ‐alanine]} (Figure 1p).…”

Section: Role Of Dual Inhibitors In Different Diseasesmentioning

confidence: 99%

Dual inhibition: a novel promising pharmacological approach for different disease conditions

Patyar

Prakash

Medhi

2011

Journal of Pharmacy and Pharmacology

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To overcome the problems associated with polypharmacy, which include medication non compliance, adverse drug reactions, drug-drug interactions and increased pill-burden, various strategies, such as sustained-release drugs and fixed-dose combination regimens (polypills), have been developed. Out of these, a novel and very much promising approach is the use of dual-action drugs. Amongst the dual-action drugs, there is a class of compounds known as dual inhibitors, which possess the dual inhibitory activity. The most common examples of dual inhibitors are rivastigmine, ladostigil, asenapine, phenserine, amitriptyline, clomipramine, doxepin and desipramine. This review article focuses on the conventional drugs used in different diseases which possess dual inhibition activity as well as those which are still in the preclinical/clinical phase.

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“…The biomarkers would be urine glucose, obtained by catheter in real time, and 18 F‐FDG excretion and reabsorption (a proxy of glucose excretion and reabsorption), or 11 C‐labeled drug as measured by dynamic PET imaging. Natriuretic peptides, vasodilation, and cGMP as biomarkers . Natriuretic peptide (analog of the naturally occurring atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)), a proposed vascular modulator with cardioprotective properties, is administered into the radial artery . Vasodilatation and cGMP concentrations serve as physical and chemical biomarkers, respectively, of drug action, and have been shown to take place within minutes of infusion .…”

Section: Introductionmentioning

confidence: 99%

Intra‐Target Microdosing (ITM): A Novel Drug Development Approach Aimed at Enabling Safer and Earlier Translation of Biological Insights Into Human Testing

Burt¹,

Noveck

Macleod

et al. 2017

Clinical Translational Sci

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Pharmacological modulation of the natriuretic peptide system

Cited by 10 publications

References 122 publications

Reversal of diabetic vasculopathy in a rat model of type 1 diabetes by opiorphin-related peptides

Reversal of diabetic vasculopathy in a rat model of type 1 diabetes by opiorphin-related peptides

Dual inhibition: a novel promising pharmacological approach for different disease conditions

Intra‐Target Microdosing (ITM): A Novel Drug Development Approach Aimed at Enabling Safer and Earlier Translation of Biological Insights Into Human Testing

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