Synthesis, biological evaluation, and preliminary structure-activity considerations of a series of alkylphenols as intravenous anesthetic agents

James, R. F. L.; Glen, J. B.

doi:10.1021/jm00186a013

Cited by 187 publications

(125 citation statements)

References 2 publications

(3 reference statements)

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…Propofol [2,6 di-isopropylphenol; (James and Glen, 1980)] is an anesthetic agent that is thought not to interfere with cerebral blood flow response and flow-metabolism coupling (Johnston et al, 2003;Veselis et al, 2005). Propofol acts mainly on GABA A receptors, potentiating GABAergic interneurons in the cortex and enhancing neuronal inhibition (Antkowiak, 1999;Franks, 2008;Brown et al, 2011).…”

Section: Methodsmentioning

confidence: 99%

Spatiotemporal Reconfiguration of Large-Scale Brain Functional Networks during Propofol-Induced Loss of Consciousness

et al. 2012

View full text Add to dashboard Cite

Applying graph theoretical analysis of spontaneous BOLD fluctuations in functional magnetic resonance imaging (fMRI), we investigated whole-brain functional connectivity of 11 healthy volunteers during wakefulness and propofol-induced loss of consciousness (PI-LOC). After extraction of regional fMRI time series from 110 cortical and subcortical regions, we applied a maximum overlap discrete wavelet transformation and investigated changes in the brain's intrinsic spatiotemporal organization. During PI-LOC, we observed a breakdown of subcortico-cortical and corticocortical connectivity. Decrease of connectivity was pronounced in thalamocortical connections, whereas no changes were found for connectivity within primary sensory cortices. Graph theoretical analyses revealed significant changes in the degree distribution and local organization metrics of brain functional networks during PI-LOC: compared with a random network, normalized clustering was significantly increased, as was small-worldness. Furthermore we observed a profound decline in long-range connections and a reduction in whole-brain spatiotemporal integration, supporting a topological reconfiguration during PI-LOC. Our findings shed light on the functional significance of intrinsic brain activity as measured by spontaneous BOLD signal fluctuations and help to understand propofol-induced loss of consciousness.

show abstract

Section: Methodsmentioning

confidence: 99%

Spatiotemporal Reconfiguration of Large-Scale Brain Functional Networks during Propofol-Induced Loss of Consciousness

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Propofol is highly membrane soluble (James & Glen, 1980) and hence may produce its effects on GABAA receptors indirectly via an interaction with the surrounding lipid membrane. In an attempt to define further the site of action of this anaesthetic the potentiating effect of bath applied propofol (1.7,UM) on GABA-evoked currents was compared in control cells and (8.4-84 pM) to a bovine chromaffin cell voltage clamped at -60mV induced a dose-dependent inward current associated with a large increase in membrane current noise.…”

Section: Propofol Modulation Of Gabaa Receptors Exhibits Membrane Asymentioning

confidence: 99%

The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurones

Hales

Lambert

1991

British J Pharmacology

328

226

View full text Add to dashboard Cite

University of Dundee, Dundee DD1 9SY1 The interaction of the intravenous general anaesthetic propofol (2,6-diisopropylphenol) with the GABAA receptor has been investigated in voltage-clamped bovine chromaffin cells and rat cortical neurones in cell culture. Additionally, the effects of propofol on the glycine and GABAA receptors of murine spinal neurones were determined. 2 Propofol (1.7-16.8 uM) reversibly and dose-dependently potentiated the amplitude of membrane currents elicited by GABA (100puM) applied locally to bovine chromaffin cells. Intracellular application of propofol (16.8 pM) was ineffective. In rat cortical neurones and murine spinal neurones, extracellular application of 8.4pM and 1.7-16.8/pM propofol respectively produced a potentiation of GABA-evoked currents qualitatively similar to that seen in the bovine chromaffin cell. 3 The potentiation by propofol (1.7,UM) was not associated with a change in the reversal potential of the GABA-evoked whole cell current. On outside-out membrane patches isolated from bovine chromaffin cells, propofol (1.7,UM) had little or no effect on the GABA single channel conductances, but greatly increased the probability of the GABA-gated channel being in the conducting state. 4 The potentiation of GABA-evoked whole cell currents by propofol (1.7 pM) was not influenced by the benzodiazepine antagonist flumazenil (0.3 pM). A concentration of propofol (1.7/pM) that substantially potentiated GABA currents had little effect on currents induced by the activation of the GABAA receptor by pentobarbitone (1 mM). 5 Bath application of propofol (8.4-252 pM), to bovine chromaffin cells voltage clamped at -60 mV, induced an inward current associated with an increase in membrane current noise on all cells sensitive to GABA. Intracellular application of propofol (16.8,UM) was ineffective in this respect. Local application of propofol (600pM) induced whole cell currents with a reversal potential dependent upon the CF-gradient across the cell membrane.6 On outside-out membrane patches formed from bovine chromaffin cells, propofol (30M) induced single channels with mean chord conductances of 29 and 12 pS. The frequency of propofol channels was greatly reduced by coapplication of 1 CM bicuculline. Under identical ionic conditions, GABA (1 pM) activated single channels with mean chord conductances of 33, 16 and 10pS.7 Bath applied propofol (0.84-16.8 juM) dose-dependently potentiated strychnine-sensitive currents evoked by glycine (100,Mm) in murine spinal neurones.8 The relevance of the present results to the general anaesthetic action of propofol is discussed.

show abstract

“…Propofol (2,6 di-isopropylphenol) is an alkylphenol used as an intravenous general anaesthetic and hypnotic (James & Glen, 1980). Since its introduction into clinical practice in the 1980's, propofol has been used extensively because of its favourable pharmacokinetic properties and limited number of side-effects (for review see Skues & Prys-Roberts, 1989;Borgeat et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Inhibition by propofol (2,6 di‐isopropylphenol) of the N‐methyl‐D‐aspartate subtype of glutamate receptor in cultured hippocampal neurones

Orser

Bertlik

Wang

et al. 1995

British J Pharmacology

224

115

View full text Add to dashboard Cite

show abstract

Synthesis, biological evaluation, and preliminary structure-activity considerations of a series of alkylphenols as intravenous anesthetic agents

Cited by 187 publications

References 2 publications

Spatiotemporal Reconfiguration of Large-Scale Brain Functional Networks during Propofol-Induced Loss of Consciousness

Spatiotemporal Reconfiguration of Large-Scale Brain Functional Networks during Propofol-Induced Loss of Consciousness

The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurones

Inhibition by propofol (2,6 di‐isopropylphenol) of the N‐methyl‐D‐aspartate subtype of glutamate receptor in cultured hippocampal neurones

Contact Info

Product

Resources

About