1. The haemodynamic profile of
elgodipine (1-30 micrograms kg-1, i.v.), a new
dihydropyridine calcium antagonist, has been compared directly with that of
nicardipine (1-30 micrograms kg-1, i.v.) in
chloralose-anaesthetized dogs. 2.
Nicardipine produced dose-related systemic, pulmonary and coronary vasodilatation accompanied by reflex
tachycardia, inotropy and increases in cardiac output and myocardial oxygen consumption (MVO2).
Elgodipine had similar
vasodilator and hypotensive properties to
nicardipine but produced less reflex inotropy, little or no reflex
tachycardia and did not increase MVO2. 3. Both
calcium antagonists were retested in a separate group of anaesthetized dogs pretreated with
propranolol (1 mg kg-1, i.v.) and
atropine (0.3 mg kg-1, i.v.) to abolish reflex autonomic tone to the heart and thus reveal the direct cardiac effects of each compound. Under these conditions both
elgodipine and
nicardipine decreased heart rate and cardiac contractility and slowed atrio-ventricular conduction.
Elgodipine was approximately ten times more potent than
nicardipine as a decelerator agent and slightly more potent in depressing cardiac contractility and increasing PR interval duration.
Elgodipine, unlike
nicardipine, slightly reduced the QTc interval of the electrocardiogram. Therefore, the potent decelerator effect of
elgodipine, which was present throughout the dose-range, appears to be largely responsible for the suppression of reflex
tachycardia observed when the baroreflex is functional. 4.
Elgodipine is a potent systemic and coronary
vasodilator with more marked direct cardiac effects than
nicardipine, particularly with respect to slowing of heart rate. The ability of
elgodipine to increase coronary blood flow without significant reflex
tachycardia or increases in MVO2 suggests that this compound will have a more favourable effect on myocardial
oxygen supply/demand balance than
nicardipine. The haemodynamic profile of
elgodipine may be suitable for the treatment of angina.