Unique pharmacologic properties of amlodipine.

Amlodipine is an intrinsically long-acting, vasoselective calcium antagonist structurally related to nifedipine, but with unique binding and pharmacologic properties that distinguish it from other agents of this class. Pharmacokinetic studies in animal models demonstrate a more prolonged half-life, high volume of distribution, and gradual elimination of amlodipine compared with that of other calcium antagonists. The presence of a basic side chain at the 2-position of the dihydropyridine ring renders the molecule > 90% ionized at physiologic pH and is believed to be primarily responsible for its markedly different pharmacologic and pharmacokinetic properties.

Cholesterol alters the binding of Ca2+ channel blockers to the membrane lipid bilayer.

X-ray diffraction and equilibrium binding techniques were used to study the effect of cholesterol on membrane binding of the charged 1,4-dihydropyridine (DHP) Ca2+ channel antagonist amlodipine and uncharged isradipine, nimodipine, and nitrendipine. Increases in membrane cholesterol content resulted in a marked decrease in DHP binding to cardiac phospholipid membranes, as expressed by the equilibrium partition coefficient (Kp[mem]). Between a 0:1 and 0.

Effects of endothelium regeneration on canine coronary artery function.

During coronary catheterization under general anesthesia, the endothelium of a portion of the proximal left circumflex coronary artery of dogs was removed (injured). Segments from the denuded and normal (distal circumflex and left anterior descending coronary) regions were removed immediately in some animals (acute studies) or 5 wk after the injury in other animals (chronic studies). No significant differences in passive mechanics or active stress normalized to medial thickness were found between segments from normal and denuded regions in acute studies or normal and injured segments in chronic studies.

Efficacy and safety of Minipress XL, a new once-a-day formulation of prazosin.

The efficacy and safety of prazosin GITS (gastro-intestinal therapeutic system), a new extended-release once-a-day formulation, were assessed both as monotherapy in mild essential hypertension and in combination with a diuretic in moderate essential hypertension in two multicenter, double-blind, placebo-controlled trials. Prazosin GITS (Minipress XL) given once daily in doses of either 10 or 20 mg significantly reduced sitting and standing systolic and diastolic blood pressure compared with placebo in both mild and moderate essential hypertension. There were minimal, clinically insignificant changes in heart rate following prazosin-GITS treatment (2.

Uterine arterial responses to arachidonate in pregnant and nonpregnant rabbits.

Several investigators have suggested that prostaglandins (PG) may play a major regulatory role in maintaining uteroplacental blood flow in pregnancy. The present study was undertaken to assess the response of the uterine artery from near-term pregnant and nonpregnant rabbits to the PG precursor Na-arachidonate (AA) (C 20:4). Isolated uterine arterial strips were equilibrated isometrically under their optimal resting tensions in physiologic salt solution.