In vitro activity: Amlodipine causes a dose-dependent increase in nitrite production. Amlodipine also increases nitrite production in large coronary arteries and in aorta. Amlodipine is attributed to distinct membrane physico-chemical interactions. Amlodipine contributes to distinct membrane biophysical interactions that lead to potent lipid antioxidant effects, independent of calcium channel modulation. Amlodipine increases plaque smooth muscle cell content (P<0.05), whereas atenolol decreases plaque inflammation. Amlodipine attenuates intracellular neuronal Ca2+ increases elicited by KCl depolarization but does not affect Ca2+ changes triggered by N-methyl-D-aspartate receptor activation. Amlodipine also inhibits free radical-induced damage to lipid constituents of the membrane in a dose-dependent manner, independent of Ca2+ channel modulation

Cell Assay: Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the movement of calcium ions into vascular smooth muscle cells and cardiac muscle cells. Experimental data suggest amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects, or decreased heart muscle contractility, can be detected in vitro, but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa = 8.6), and its interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.

J Mol Cell Cardiol. 1999 Jan;31(1):275-81; J Hypertens. 1998 Apr;16(4):457-66