Document Detail

Herbal monoterpene alcohols inhibit propofol metabolism and prolong anesthesia time.
MedLine Citation:
PMID:  16436284     Owner:  NLM     Status:  MEDLINE    
2,6-Diisopropylphenol (Propofol) is a short-acting intravenous anesthetic that is rapidly metabolized by glucuronidation and ring hydroxylation catalyzed by cytochrome P450. The goal of this research was to determine whether dietary monoterpene alcohols (MAs) could be used to prolong the anesthetic effect of propofol by inhibiting propofol metabolism in animals. Mice were injected intraperitoneally (i.p.) with MAs (100-200) mg/kg followed by the administration of 100 mg/kg propofol 40 min later via an i.p. injection. The time of the anesthesia of each mouse was recorded. It was found that (+/-)-borneol, (-)-carveol, trans-sobrerol, and menthol significantly extended the anesthetic effect of propofol (>3 times). The concentration of propofol in the mouse blood over time (up to 180 min) also increased in mice pre-treated with (-)-borneol, (-)-carveol, and trans-sobrerol. The volume of distribution of propofol decreased in the (-)-borneol (p<0.05), pre-treated group as compared to the propofol control group. Moreover, the maximum blood concentration of propofol and the concentration of propofol in the blood as indicated by the area under the curve were significantly increased in (-)-borneol and (-)-carveol pre-treated groups. Additional evidence using rat hepatocytes showed that (-)-borneol inhibited propofol glucuronidation whereas trans-sobrerol and (-)-carveol inhibited cytochrome P450 dependent microsomal aminopyrine N-demethylation. These results suggest that (-)-borneol extends propofol-induced anesthesia by inhibiting its glucuronidation in the mouse whereas trans-sobrerol (-)-carveol extends propofol-induced anesthesia by inhibiting P450 catalyzed propofol metabolism.
Alison Li Lin; Nandita Shangari; Tom S Chan; Diadelas Remirez; Peter J O'Brien
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-01-24
Journal Detail:
Title:  Life sciences     Volume:  79     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-05-22     Completed Date:  2006-06-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  21-9     Citation Subset:  IM    
Pharmaceutical Sciences Department, University of Toronto, 19 Russell Street, Toronto, Ontario, M5S 2S2, Canada.
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MeSH Terms
Alcohols / pharmacology*
Aminopyrine N-Demethylase / metabolism
Anesthetics, Intravenous / pharmacokinetics*
Bornanes / pharmacology
Chromatography, High Pressure Liquid
Cytochrome P-450 Enzyme System / metabolism
Dose-Response Relationship, Drug
Glucuronides / metabolism
Hepatocytes / drug effects,  metabolism
Liver / metabolism
Microsomes, Liver / drug effects,  metabolism
Monoterpenes / pharmacology*
Propofol / pharmacokinetics*
Rats, Sprague-Dawley
Terpenes / pharmacology
Reg. No./Substance:
0/Alcohols; 0/Anesthetics, Intravenous; 0/Bornanes; 0/Glucuronides; 0/Monoterpenes; 0/Terpenes; 10385-78-1/isoborneol; 2078-54-8/Propofol; 498-71-5/sobrerol; 9035-51-2/Cytochrome P-450 Enzyme System; 99-48-9/carveol; EC 1.5.3.-/Aminopyrine N-Demethylase

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

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