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Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

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In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
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The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
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Renal clearance plays a pivotal role in drug elimination from the body and can be influenced by drug distribution and interactions. Understanding these factors is crucial in pharmacology as they impact the effectiveness and duration of drug therapy.
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The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
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Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
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Liddle syndrome is a genetically inherited form of hypertension characterized by the overactivity of epithelial sodium channels in the nephron, the functional unit of the kidney. This heightened activity leads to increased sodium reabsorption and excessive excretion of potassium. To counteract this, potassium-sparing diuretics such as amiloride are used. They function by blocking these sodium channels, thereby reducing the influx of sodium into the epithelial cells and minimizing the loss of...
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Losartan Interactions with 2-Hydroxypropyl-β-CD.

Vasiliki Palli1, Georgios Leonis1, Nikoletta Zoupanou1

  • 1Department of Chemistry, School of Sciences, National and Kapodistrian University of Athens, 15784 Athens, Greece.

Molecules (Basel, Switzerland)
|April 23, 2022
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Summary

Losartan potassium salt (LSR) complexed with 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) shows improved properties. Molecular interactions confirmed favorable and reversible complexation, suggesting further biological study for this antihypertensive formulation.

Keywords:
differential scanning calorimetryhydroxypropyl-β-cyclodextrinlosartanmolecular dynamicsmolecular interactionsnuclear magnetic resonance

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Area of Science:

  • Pharmaceutical Sciences
  • Physical Chemistry
  • Materials Science

Background:

  • Losartan potassium salt (LSR) is a widely used antihypertensive medication.
  • Formulating LSR with 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) may enhance its pharmacological activity.
  • Understanding the molecular interactions is crucial for optimizing drug delivery and efficacy.

Purpose of the Study:

  • To investigate the molecular interactions between losartan potassium salt and 2-hydroxypropyl-β-cyclodextrin.
  • To confirm the complexation and evaluate its properties using various analytical techniques.
  • To provide evidence for the potential of this new formulation in pharmaceutical applications.

Main Methods:

  • Differential Scanning Calorimetry (DSC) to analyze thermal properties and complexation.
  • Nuclear Magnetic Resonance (NMR) spectroscopy (chemical shift and T1 values) to confirm complexation.
  • Molecular Dynamics (MD) simulations to study the reversibility and nature of the complexation.

Main Results:

  • DSC indicated distinct thermal properties for the lyophilized LSR/2-HP-β-CD complex compared to a simple mixture.
  • NMR studies confirmed complexation through observed chemical shift changes and altered T1 values.
  • MD calculations demonstrated a reversible and favorable complexation between LSR and 2-HP-β-CD.

Conclusions:

  • The study provides strong evidence of molecular complexation between losartan potassium salt and 2-hydroxypropyl-β-cyclodextrin.
  • The observed favorable and reversible complexation suggests potential for improved pharmacological profiles.
  • This LSR/2-HP-β-CD formulation warrants further investigation through biological experiments for its antihypertensive potential.