Abstract
We synthesized 2,6-diisopropyl-4-[3-(3-methyl-3H-diazirin-3-yl)propyl]phenol (p-(4-azipentyl)propofol), or p-4-AziC5-Pro, a novel photoactivable derivative of the general anesthetic propofol. p-4-AziC5-Pro has an anesthetic potency similar to that of propofol. Like propofol, the compound potentiates inhibitory GABA(A) receptor current responses and allosterically modulates binding to both agonist and benzodiazepine sites, assayed on heterologously expressed GABA(A) receptors. p-4-AziC5-Pro inhibits excitatory current responses of nACh receptors expressed in Xenopus oocytes and photoincorporates into native nACh receptor-enriched Torpedo membranes. Thus, p-4-AziC5-Pro is a functional general anesthetic that both modulates and photoincorporates into Cys-loop ligand-gated ion channels, making it an excellent candidate for use in identifying propofol binding sites.
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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Allosteric Regulation
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Anesthetics, General / chemical synthesis*
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Anesthetics, General / chemistry
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Anesthetics, General / pharmacology
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Animals
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Binding Sites
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Diazomethane / analogs & derivatives*
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Diazomethane / chemical synthesis
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Diazomethane / chemistry
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Diazomethane / pharmacology
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Female
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Humans
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Ion Channel Gating
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Larva
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Ligands
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Nicotinic Antagonists / chemical synthesis
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Nicotinic Antagonists / chemistry
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Nicotinic Antagonists / pharmacology
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Oocytes / drug effects
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Oocytes / physiology
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Photoaffinity Labels / chemical synthesis*
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Photoaffinity Labels / chemistry
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Propofol / analogs & derivatives*
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Propofol / chemical synthesis*
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Propofol / chemistry
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Propofol / pharmacology
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Receptors, GABA-A / physiology*
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Receptors, Nicotinic / physiology
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Solubility
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Torpedo
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Xenopus laevis
Substances
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2,6-diisopropyl-4-(3-(3-methyl-3H-diazirin-3-yl)propyl)phenol
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Anesthetics, General
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Ligands
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Nicotinic Antagonists
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Photoaffinity Labels
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Receptors, GABA-A
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Receptors, Nicotinic
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Diazomethane
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Propofol