Document Detail

MCl-176, a novel calcium channel blocker, attenuates the ischemic myocardial acidosis induced by coronary artery occlusion in dogs.
MedLine Citation:
PMID:  3361449     Owner:  NLM     Status:  MEDLINE    
The effect of MCl-176 [2-(2,5-dimethoxyphenylmethyl)-3-(2-dimethylaminoethyl)-6- isopropoxy-4(3H)-quinazolinone hydrochloride], a novel calcium channel blocker, on ischemic myocardial acidosis was studied in the dog heart, in which the left anterior descending coronary artery was partially occluded for 90 min (partial occlusion). Myocardial pH (measured by a micro glass pH electrode) was about 7.60 in the nonischemic normal heart. The myocardial pH decreased rapidly in response to partial occlusion, and reached the steady state of about 6.85 within 30 min (i.e., the myocardial [H+] increased after partial occlusion). Saline or drug was injected i.v. 30 min after partial occlusion, and the drug effect was observed till the end of partial occlusion. Myocardial [H+], that had been increased by partial occlusion, restored slightly after the saline injection, and the restoration was about 30% 60 min after the injection. MCl-176 increased this spontaneous restoration of myocardial [H+] with a decrease in blood pressure and heart rate; the restoration induced by 0.1 mg/kg of MCl-176 was 74% 60 min after the injection. Even in the paced heart, MCl-176 (0.1 mg/kg) attenuated the ischemia-induced myocardial acidosis. Propranolol (1 mg/kg) also attenuated the myocardial acidosis, the restoration being 82%. These results indicate that MCl-176 attenuates the myocardial acidosis during ischemia as does propranolol, and that the mechanism of action of MCl-176 is not due primarily to a decrease in heart rate.
Y Hara; K Ichihara; Y Abiko
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  245     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1988 Apr 
Date Detail:
Created Date:  1988-06-02     Completed Date:  1988-06-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  305-10     Citation Subset:  IM    
Department of Pharmacology, Asahikawa Medical College, Japan.
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MeSH Terms
Acidosis / etiology*
Arterial Occlusive Diseases / complications*
Calcium Channel Blockers / pharmacology*
Coronary Vessels
Heart / drug effects
Hydrogen-Ion Concentration
Myocardial Infarction / complications*
Propranolol / pharmacology
Quinazolines / pharmacology*
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Quinazolines; 0/Quinazolinones; 103315-31-7/MCI 176; 525-66-6/Propranolol

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

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