Amlodipine besylate mechanism of action
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Calcium Channel Blockade and Vascular Smooth Muscle Relaxation
Amlodipine besylate is a synthetic dihydropyridine calcium channel blocker. Its main mechanism of action is the inhibition of L-type calcium channels in the smooth muscle cells of blood vessels. By blocking these channels, amlodipine reduces the influx of calcium ions, leading to relaxation of vascular smooth muscle, vasodilation, and a subsequent decrease in blood pressure. This effect is more pronounced in arterial vascular smooth muscle than in cardiac tissue, making it especially effective for treating hypertension and angina Hussan2019Ahsan2018.
Selectivity and Cardiovascular Effects
Amlodipine besylate is highly selective for arterial smooth muscle, which helps lower blood pressure without significantly affecting heart rate or contractility. It also has a negative inotropic effect, meaning it can reduce the force of heart muscle contraction, which decreases the workload on the heart .
Additional Molecular and Cellular Mechanisms
Recent studies suggest that amlodipine besylate may have additional mechanisms beyond calcium channel blockade. For example, it has been shown to interact with GABA A receptors in the brain, although this effect is less pronounced than with some related compounds. This interaction may contribute to its vasodilatory effects, especially under conditions like cerebral ischemia .
Amlodipine besylate also acts as a GPR40 agonist, which can help alleviate diabetic peripheral neuropathy by reducing inflammation and improving mitochondrial function in nerve cells. This involves the GPR40/β-arrestin2/NLRP3 and GPR40/LKB1/AMPK/SIRT1/PGC-1α pathways, which help protect nerve cells and improve their function .
Antioxidant Properties
Computational and molecular docking studies indicate that amlodipine besylate has antioxidant properties. It can interact with enzymes like monoamine oxidase B, suggesting a potential role in reducing oxidative stress, which may contribute to its therapeutic effects .
Effects on Renal Function and Signaling Pathways
Amlodipine besylate can also improve kidney function in patients with hypertension and renal failure. It does this by regulating the PI3K/AKT signaling pathway, which helps reduce blood pressure and improve biochemical markers of kidney health. This pathway is involved in cell survival and inflammation, and its activation by amlodipine may help protect kidney tissue .
Physicochemical Properties and Drug Transport
Studies on the physicochemical properties of amlodipine besylate show that its structure and interactions in solution can affect how it is transported across biological membranes. These properties may influence its absorption and distribution in the body, further supporting its effectiveness as an antihypertensive agent .
Conclusion
Amlodipine besylate primarily works by blocking L-type calcium channels in vascular smooth muscle, leading to vasodilation and reduced blood pressure. It is highly selective for arterial smooth muscle, has additional effects on GABA A receptors and GPR40, and may offer antioxidant and kidney-protective benefits through various molecular pathways. These combined actions make it a widely used and effective medication for hypertension and angina Ким2017Hussan2019Wei2025+3 MORE.
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ГАМК А -рецепторные механизмы противоишемического цереброваскулярного эффекта S-амлодипина никотината
S-amlodipine nicotinate enhances blood supply to damaged brains more effectively than amlodipine besylate, with a GABA-ergic mechanism of action.
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