The hemodynamic properties of amlodipine in anesthetised and conscious dogs: comparison with nitrendipine and influence of beta-adrenergic blockade.
The hemodynamic actions of the new dihydropyridine calcium-channel blocker amlodipine were assessed and compared with those of nitrendipine using anesthetised dogs and were also investigated in conscious dogs with and without beta-adrenergic blockade. After bolus intravenous administration, amlodipine (25 to 1600 micrograms/kg) or nitrendipine (1 to 128 micrograms/kg) was administered to anesthetised dogs at 30-minute intervals, caused dose-related reductions in systemic and coronary vascular resistances with corresponding increases in cardiac output and coronary flow. Nitrendipine, unlike amlodipine, caused marked acute hypotension. The onset of action of amlodipine was markedly slower than that of nitrendipine, and effects were maintained for 30 minutes--recovery from nitrendipine was largely complete at 30 minutes. In conscious dogs, amlodipine (250, 500, 1000 micrograms/kg IV) caused dose-related reductions in systemic vascular resistance that approached maximum within 5 minutes and persisted for over 4 hours. Reflex increases in heart rate, cardiac output, and cardiac contractility were attenuated by prior treatment with propranolol, resulting in earlier and greater falls in blood pressure, but no marked adverse effects on cardiac contraction or conduction. In the absence of propranolol, maximum falls in blood pressure occurred 3 to 4 hours after the dose, possibly as a result of the changed baroceptor sensitivity induced by amlodipine. These results show amlodipine to have the basic hemodynamic profile of other dihydropyridine calcium-channel blockers, but in addition it demonstrates a slower onset and longer duration of action; the reasons behind these pharmacodynamic properties are discussed.
Dodd
M G
MG
Discovery Biology Department, Pfizer Central Research, Sandwich, Kent, England.
Gardiner
D G
DG
Carter
A J
AJ
Sutton
M R
MR
Burges
R A
RA
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D017311:Amlodipine; D000758:Anesthesia; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D017311:Amlodipine; D009568:Nitrendipine; D011433:Propranolol; D009543:Nifedipine