Pharmacologic profile of amlodipine.
Amlodipine is a potent calcium antagonist, inhibiting Ca2+-induced contractions of depolarized rat aorta with an IC50 of 1.9 nM. Unlike nifedipine, it displayed very slow association and dissociation with the calcium channel. The ability of amlodipine to inhibit Ca2+-induced contractions was strongly dependent on the K+ concentration present before the contraction, suggesting marked voltage dependence of action. Radioligand-binding studies in cardiac membrane preparations suggested that amlodipine may interact directly with both 1,4-dihydropyridine and diltiazem-binding sites on the calcium channel. Hemodynamic studies in anesthetized and conscious dogs showed that amlodipine is a coronary and peripheral vasodilator with a slow onset and long duration of effect, even when given by intravenous injection; the reflex stimulation of cardiac output, heart rate and myocardial contractility induced by amlodipine was attenuated by propranolol, but no marked negative inotropic or dromotropic effects were observed. Amlodipine was an effective oral antihypertensive agent in rat and dog models of hypertension, and its 24-hour duration of action in hypertensive dogs correlated well with its long plasma half-life in this species. The natriuretic properties displayed by amlodipine may contribute to its use as a first-line drug for the treatment of hypertension.
Burges
R A
RA
Department Discovery Biology, Pfizer Central Research, Sandwich, Kent, United Kingdom.
Dodd
M G
MG
Gardiner
D G
DG
D000284:Administration, Oral; D017311:Amlodipine; D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents; D001665:Binding Sites; D002121:Calcium Channel Blockers; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D017311:Amlodipine; D009543:Nifedipine