Abstract
The use of isotopic substitution to delay the oxidative metabolism of the anesthetic propofol 1 was studied. The aromatic hydrogens of propofol 1 were replaced by deuterium to produce the mono- and trideuterated derivatives 4 and 5. In vitro metabolic studies on human hepatic microsomes showed no isotopic effect in the para hydroxylation of propofol, and 1, 4, and 5 display similar hypnotic activity and toxicity in mice.
MeSH terms
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Anesthetics, Intravenous / metabolism*
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Anesthetics, Intravenous / pharmacology*
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Anesthetics, Intravenous / toxicity
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Animals
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Deuterium
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Gas Chromatography-Mass Spectrometry
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Humans
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Hypnotics and Sedatives / pharmacology
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Hypnotics and Sedatives / toxicity
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In Vitro Techniques
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Mice
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Microsomes, Liver / drug effects
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Microsomes, Liver / metabolism
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Propofol / metabolism*
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Propofol / pharmacology*
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Propofol / toxicity
Substances
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Anesthetics, Intravenous
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Hypnotics and Sedatives
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Deuterium
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Propofol