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M-Azipropofol (AziPm) a photoactive analogue of the intravenous general anesthetic propofol.

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.

SUBMITTER: Hall MA

PROVIDER: S-EPMC2917171 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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m-Azipropofol (AziPm) a photoactive analogue of the intravenous general anesthetic propofol.

Hall Michael A MA Xi Jin J Lor Chong C Dai Shuiping S Pearce Robert R Dailey William P WP Eckenhoff Roderic G RG

Journal of medicinal chemistry 20100801 15

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 ...[more]

PMID: 20597506

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| S-EPMC5448234 | biostudies-literature

Direct visualization of general anesthetic propofol on neurons by stimulated Raman scattering microscopy.

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| S-EPMC4936777 | biostudies-literature

The influence of moderate or deep neuromuscular block status on anesthetic depth monitoring system during total intravenous anesthesia using propofol and remifentanil: A randomized trial.

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| S-EPMC10454749 | biostudies-literature

Anesthetic propofol attenuates the isoflurane-induced caspase-3 activation and A? oligomerization.

Project description:Accumulation and deposition of ?-amyloid protein (A?) are the hallmark features of Alzheimer's disease. The inhalation anesthetic isoflurane has been shown to induce caspase activation and increase A? accumulation. In addition, recent studies suggest that isoflurane may directly promote the formation of cytotoxic soluble A? oligomers, which are thought to be the key pathological species in AD. In contrast, propofol, the most commonly used intravenous anesthetic, has been reported to have neuroprotective effects. We therefore set out to compare the effects of isoflurane and propofol alone and in combination on caspase-3 activation and A? oligomerization in vitro and in vivo. Naïve and stably-transfected H4 human neuroglioma cells that express human amyloid precursor protein, the precursor for A?; neonatal mice; and conditioned cell culture media containing secreted human A?40 or A?42 were treated with isoflurane and/or propofol. Here we show for the first time that propofol can attenuate isoflurane-induced caspase-3 activation in cultured cells and in the brain tissues of neonatal mice. Furthermore, propofol-mediated caspase inhibition occurred when there were elevated levels of A?. Finally, isoflurane alone induces A?42, but not A?40, oligomerization, and propofol can inhibit the isoflurane-mediated oligomerization of A?42. These data suggest that propofol may mitigate the caspase-3 activation by attenuating the isoflurane-induced A?42 oligomerization. Our findings provide novel insights into the possible mechanisms of isoflurane-induced neurotoxicity that may aid in the development of strategies to minimize potential adverse effects associated with the administration of anesthetics to patients.

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