Abstract
Propofol is the most commonly used sedative-hypnotic drug for noxious procedures, yet the molecular targets underlying either its beneficial or toxic effects remain uncertain. In order to determine targets and thereby mechanisms of propofol, we have synthesized a photoactivateable analogue by substituting an alkyldiazirinyl moiety for one of the isopropyl arms but in the meta position. m-Azipropofol retains the physical, biochemical, GABA(A) receptor modulatory, and in vivo activity of propofol and photoadducts to amino acid residues in known propofol binding sites in natural proteins. Using either mass spectrometry or radiolabeling, this reagent may be used to reveal sites and targets that underlie the mechanism of both the desirable and undesirable actions of this important clinical compound.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anesthetics, Intravenous / chemical synthesis*
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Anesthetics, Intravenous / pharmacology
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Animals
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Apoferritins / chemistry
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Cell Line
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Diazomethane / analogs & derivatives*
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Diazomethane / chemical synthesis
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Diazomethane / pharmacology
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Electrophysiology
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Horses
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Humans
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Hypnotics and Sedatives / chemical synthesis*
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Hypnotics and Sedatives / pharmacology
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Larva
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Models, Molecular
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Motor Activity / drug effects
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Photoaffinity Labels / chemical synthesis*
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Photoaffinity Labels / pharmacology
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Propofol / analogs & derivatives*
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Propofol / chemical synthesis*
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Propofol / pharmacology
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Protein Binding
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Protein Subunits / physiology
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Receptors, GABA-A / physiology
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Reflex, Startle / drug effects
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Structure-Activity Relationship
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Xenopus laevis
Substances
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2-isopropyl-5-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenol
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Anesthetics, Intravenous
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Hypnotics and Sedatives
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Photoaffinity Labels
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Protein Subunits
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Receptors, GABA-A
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Diazomethane
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Apoferritins
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Propofol