Document Detail

The comparative toxicity of cocaine and its metabolites in conscious rats.
MedLine Citation:
PMID:  10360867     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The metabolites of cocaine, benzoylecgonine and ecgonine methyl ester, have been considered pharmacologically inactive when administered systemically. However, recent in vitro studies suggest that this may not be true. The current study was designed to evaluate the systemic toxicity of cocaine and its metabolites when administered systemically to awake rats fitted with catheters for long-term monitoring. METHODS: Cocaine, norcocaine, cocaethylene, benzoylecgonine, and ecgonine methyl ester were infused intravenously to produce sequential behavioral alterations and central nervous system and cardiovascular toxic effects. Arterial blood pressure and heart rate were monitored continuously. Plasma and tissue samples were analyzed for all compounds by capillary gas chromatography-mass spectrometry. RESULTS: The dose of norcocaine necessary to produce toxic effects was smaller than that of cocaine and cocaethylene. Benzoylecgonine and ecgonine methyl ester did not produce toxic manifestations at infusion rates that produced toxicity in the cocaine, norcocaine, and cocaethylene groups. Furthermore, 30- and 60-fold higher doses of benzoylecgonine and ecgonine methyl ester, respectively, were necessary to produce only mild neurobehavioral changes. Benzoylecgonine was not lethal even at doses 100 times greater than cocaine. CONCLUSIONS: These results indicate that benzoylecgonine and ecgonine methyl ester are not as toxic as cocaine, norcocaine, or cocaethylene when administered intravenously to pharmacologically naive rats.
H O Morishima; R A Whittington; A Iso; T B Cooper
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Anesthesiology     Volume:  90     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  1999 Jun 
Date Detail:
Created Date:  1999-06-17     Completed Date:  1999-06-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1684-90     Citation Subset:  AIM; IM    
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
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MeSH Terms
Blood Pressure / drug effects
Cocaine / analogs & derivatives*,  pharmacokinetics,  toxicity*
Heart Rate / drug effects
Rats, Sprague-Dawley
Grant Support
Reg. No./Substance:
18717-72-1/norcocaine; 50-36-2/Cocaine; 519-09-5/benzoylecgonine; 529-38-4/cocaethylene; 7143-09-1/ecgonine methyl ester

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