p-(4-Azipentyl)propofol: a potent photoreactive general anesthetic derivative of propofol.

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Stewart DS, Savechenkov PY, Dostalova Z, Chiara DC, Ge R, Raines DE, Cohen JB, Forman SA, Bruzik KS, Miller KW

p-(4-Azipentyl)propofol: a potent photoreactive general anesthetic derivative of propofol.

J Med Chem. 2011 Dec 8;54(23):8124-35. doi: 10.1021/jm200943f. Epub 2011 Nov 10.

PubMed ID
22029276 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
MuscimolGamma-aminobutyric acid receptor subunit alpha-1ProteinHumans
Unknown
Not AvailableDetails
MuscimolGamma-aminobutyric acid receptor subunit beta-3ProteinHumans
Unknown
Not AvailableDetails
MuscimolGamma-aminobutyric acid receptor subunit gamma-2ProteinHumans
Unknown
Not AvailableDetails