Document Detail


Cardiovascular effects of cocaine: enhancement by yohimbine and atropine.
MedLine Citation:
PMID:  2913288     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cardiovascular effects of cocaine, alone and in combination with yohimbine and/or atropine, were studied in dogs anesthetized with pentobarbital sodium. All dogs were instrumented for the measurement of arterial blood pressure, left ventricular contractile force, left circumflex coronary artery blood flow, lead II ECG and heart rate. Dogs were divided into two groups; one group received no pretreatment, the other group was pretreated with atropine sulfate, 2 mg/kg. Both groups received two i.v. doses of cocaine, 1 mg/kg, approximately 3.5 hr apart. Thirty minutes before administration of the second cocaine dose, yohimbine, 0.25 mg/kg, i.v. was administered. In control animals which did not receive atropine or yohimbine, there was no difference in the cardiovascular responses to the two cocaine doses administered on this schedule. Administration of cocaine alone increased mean arterial blood pressure 9.6 +/- 2.2 mm Hg and increased the rate-pressure product, an index of myocardial oxygen consumption, 12.6 +/- 4.7%. Coronary blood flow was increased 13.1 +/- 4%. Yohimbine pretreatment significantly enhanced the cardiovascular actions of cocaine and this enhancement was most pronounced in the presence of atropine. When cocaine was administered after treatment with both atropine and yohimbine, mean arterial blood pressure was increased 44.2 +/- 7.2 mm Hg, heart rate was increased 30 +/- 7.9 beats/min and the rate-pressure product was increased by 72 +/- 10.1%, whereas coronary blood flow was increased only 42.8 +/- 12%. These data suggest that presynaptic alpha adrenergic and cholinergic muscarinic blockade may significantly increase the risk of cocaine-induced cardiovascular toxicity.
Authors:
R D Wilkerson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  248     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1989 Jan 
Date Detail:
Created Date:  1989-03-03     Completed Date:  1989-03-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  57-61     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Medical College of Ohio, Toledo.
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MeSH Terms
Descriptor/Qualifier:
Animals
Atropine / pharmacology*
Blood Pressure / drug effects
Cardiovascular System / drug effects*
Cocaine / pharmacology*
Coronary Circulation / drug effects
Dogs
Heart Rate / drug effects
Myocardial Contraction / drug effects
N-Methylscopolamine
Norepinephrine / metabolism
Oxygen Consumption / drug effects
Scopolamine Derivatives / pharmacology
Yohimbine / pharmacology*
Grant Support
ID/Acronym/Agency:
DA 04038/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Scopolamine Derivatives; 13265-10-6/N-Methylscopolamine; 146-48-5/Yohimbine; 50-36-2/Cocaine; 51-41-2/Norepinephrine; 51-55-8/Atropine

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


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