Document Detail

In vivo inhibition of platelet aggregation and occlusive coronary thrombus formation by a new calcium antagonist (R023-6152).
MedLine Citation:
PMID:  1724526     Owner:  NLM     Status:  MEDLINE    
Reports have shown that all three major classes of calcium antagonists can inhibit platelet aggregation in vitro. In this study, we compared the platelet antiaggregatory effects of R023-6152, a thiazepinone-type calcium antagonist, with diltiazem in an in vivo canine model of spontaneous coronary thrombosis. Plasma serotonin (5-HT) levels measured in the coronary sinus were used as an index of in vivo platelet aggregation and coronary flow measured by a Doppler flow probe. Untreated controls developed total coronary occlusion in 62 +/- 18 min after the current used to initiate thrombus formation was discontinued. Control 5-HT levels peaked at 213 +/- 63 ng/ml just before occlusion. Dogs receiving intravenous (i.v.) R023-6152 (200 micrograms/kg) or diltiazem (50 micrograms/kg) immediately after the current was discontinued exhibited no significant elevations in 5-HT values (12.3 +/- 1.4 and 1.84 +/- 0.42 ng/ml for R023-6152 and diltiazem, respectively) or development of coronary occlusions in the next 3 h. Small, transient decreases in arterial pressure (8-10 mm Hg) and changes in contractility occurred during infusion of both drugs. Gravimetric determinations of thrombus weights showed significantly smaller thrombi in the drug-treated animals as compared with controls. The results indicate that both R023-6152 and diltiazem are effective in suppressing in vivo platelet aggregation associated with occlusive coronary thrombus formation.
L A Sordahl; K A Rex; C R Benedict
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  18     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1991 Oct 
Date Detail:
Created Date:  1992-04-07     Completed Date:  1992-04-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  504-10     Citation Subset:  IM    
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
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MeSH Terms
Blood Pressure / drug effects
Calcium Channel Blockers / pharmacology*
Coronary Thrombosis / physiopathology,  prevention & control*
Diltiazem / analogs & derivatives*,  pharmacology
Fibrinolytic Agents / pharmacology*
Heart Rate / drug effects
Platelet Aggregation / drug effects*
Platelet Aggregation Inhibitors / pharmacology*
Serotonin / blood
Grant Support
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Fibrinolytic Agents; 0/Platelet Aggregation Inhibitors; 108383-96-6/RO 23-6152; 42399-41-7/Diltiazem; 50-67-9/Serotonin

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