Document Detail

Chronotropic effects of azelnidipine, a slow- and long-acting dihydropyridine-type calcium channel blocker, in anesthetized dogs: a comparison with amlodipine.
MedLine Citation:
PMID:  19295444     Owner:  NLM     Status:  MEDLINE    
Azelnidipine, a dihydropyridine calcium channel blocker unlike other dihydropyridine calcium channel blockers, does not increase but slightly decreases heart rate (HR) in clinical settings. In the present study, the mechanism for the HR-lowering action characteristic of azelnidipine was investigated in anesthetized dogs. In the in situ perfused sinus node preparation, the negative chronotropic action of azelnidipine was almost 5 times more potent than that of amlodipine. When injected intravenously in intact anesthetized dogs, both drugs produced a long-lasting blood pressure reduction, but the action of azelnidipine developed more slowly than that of amlodipine. Azelnidipine hardly affected HR at lower doses and decreased HR at higher doses. On the other hand, amlodipine consistently induced slight tachycardia. The HR-lowering effect of azelnidipine in autonomically blocked dogs was not much different from that in intact dogs, whereas tachycardia induced by amlodipine was eliminated in autonomically blocked dogs. However, neither drug affected the HR gain of baroreceptor reflex induced by changing carotid sinus pressure. These results suggest that compared with amlodipine, azelnidipine has a greater intrinsic negative chronotropic action and induces a lower level of reflex tachycardia most probably due to a slower development of blood pressure-lowering effects and that these characteristics of azelnidipine underlies its HR-lowering effects when administered systemically.
Michio Fujisawa; Ryosuke Yorikane; Shigetoshi Chiba; Hiroyuki Koike
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  53     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-27     Completed Date:  2009-07-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  325-32     Citation Subset:  IM    
Biological Research Laboratories, Daiichi Sankyo Co, Ltd, Tokyo, Japan.
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MeSH Terms
Adjuvants, Anesthesia / administration & dosage
Amlodipine / pharmacology*
Atropine / administration & dosage,  pharmacology
Azetidinecarboxylic Acid / analogs & derivatives*,  pharmacology
Baroreflex / drug effects
Blood Pressure / drug effects
Calcium Channel Blockers / pharmacology*
Circadian Rhythm / drug effects*
Coronary Vessels
Dihydropyridines / pharmacology*
Dose-Response Relationship, Drug
Heart Rate / drug effects
Infusions, Intravenous
Injections, Intravenous
Pentobarbital / administration & dosage
Propranolol / pharmacology
Sympathetic Nervous System / drug effects
Time Factors
Reg. No./Substance:
0/Adjuvants, Anesthesia; 0/Calcium Channel Blockers; 0/Dihydropyridines; 123524-52-7/azelnidipine; 2517-04-6/Azetidinecarboxylic Acid; 51-55-8/Atropine; 525-66-6/Propranolol; 76-74-4/Pentobarbital; 88150-42-9/Amlodipine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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