High-affinity block of voltage-operated rat IIA neuronal sodium channels by 2,6 di-tert-butylphenol, a propofol analogue

  title={High-affinity block of voltage-operated rat IIA neuronal sodium channels by 2,6 di-tert-butylphenol, a propofol analogue},
  author={Gertrud Haeseler and Martin Leuwer},
  journal={European Journal of Anaesthesiology},
Background and objective: Propofol is a phenol derivative (2,6 di-isopropylphenol) with a unique effect profile including activating effects on GABAA and blocking effects on voltage-operated sodium channels. If the substituents in the 2- and the 6-positions are replaced by tert-butyl groups, the resulting phenol derivative, 2,6 di-tert-butylphenol, despite being a close structural propofol analogue, completely lacks GABAA receptor effects. The aim of this in vitro study was to investigate the… 
Propofol inhibits the voltage-gated sodium channel NaChBac at multiple sites
In vitro and in vivo measurements show that 4-fluoropropofol and propofol have similar effects on NaChBac function and nearly identical anesthetizing effects on tadpole mobility, and the molecular basis for understanding the net inhibitory action of prop ofol on NaV channels is provided.
HCN1 Channels as Targets for Anesthetic and Nonanesthetic Propofol Analogs in the Amelioration of Mechanical and Thermal Hyperalgesia in a Mouse Model of Neuropathic Pain
In a peripheral nerve ligation model of neuropathic pain, 2,6-DTBP and subhypnotic propofol are antihyperalgesic and suggest that antagonism of central HCN1 channels may be of limited importance to general anesthesia.
Nav channel mechanosensitivity: activation and inactivation accelerate reversibly with stretch.
It is noteworthy that at voltages near the activation threshold, moderate stretch increased the peak I(Na) amplitude approximately 1.5-fold, which will be important to determine whether stretch-modulated Nav current contributes to cardiac arrhythmias, to mechanosensory responses in interstitial cells of Cajal, to touch receptor responses, and to neuropathic and/or normal pain reception.
Effects of propofol on conditioned place preference in male rats: Involvement of nitrergic system
The results suggest that propofol produces CPP effects in rats and that NO-related mechanisms may be responsible for prop ofol-induced CPP.
High‐affinity blockade of voltage‐operated skeletal muscle and neuronal sodium channels by halogenated propofol analogues
The clinical use of local anaesthetics is still limited by severe side effects, in particular, arrhythmias and convulsions, which render the search for new local anaesthetic-like action a matter of high interest.
Opioid induced hyperalgesia altered with propofol infusion.
This clinical case demonstrates that Propofol could possibly have antihyperalgesic effects on opioid induced hyperalgesia caused by high-doses of chronic opioids and worsened by fentanyl.
Effect of cholinergic crisis on the potency of different emergency anaesthesia protocols in soman-poisoned rats
Despite severe cholinergic crisis, sufficient anaesthetic depth could be achieved in all animals and did not confirm concerns of altered potency of existing anaesthetic protocols for the application of propofol or thiopental with fentanyl due to soman poisoning.
The Effects of Etomidate and Propofol Induction on Hemodynamic and Endocrine Response in Patients Undergoing Coronary Artery Bypass Graft Surgery on Cardiopulmonary Bypass
Serum cortisol levels in both groups are well above the baseline at twenty-four hours without any untoward effects, and etomidate provides more stable hemodynamic parameters when used for induction of anesthesia as compared to propofol.
The comparison of preemptive effects of propofol, remifentanil and ketamine on post-operative pain scores and analgesic requirements in elective lower abdominal surgery under general anesthesia: A randomized, double-blinded study
  • K. Naghibi, P. Kashefi, A. Abtahi
  • Medicine, Biology
    Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences
  • 2013
The pain scores were significantly lower in remifentanil group immediately after recovery and also at 2 and 6 h post-operatively, but it reversed at 12 and 24 h after recovery comparing with propofol and ketamine.


Suppression of central nervous system sodium channels by propofol.
In these experiments with pharmacologically unaltered sodium channels, propofol inhibition of currents occurred at concentrations about eight-fold above clinical plasma levels and thus at brain concentrations reached during clinical anesthesia, indicating a possible role for sodium-channel suppression in prop ofol anesthesia.
Propofol Blocks Human Skeletal Muscle Sodium Channels in a Voltage-Dependent Manner
It is suggested that propofol significantly blocks sarcolemmal sodium channels at clinically relevant concentrations while maintaining potentials close to the physiological resting potential.
Voltage- and frequency-dependent pentobarbital suppression of brain and muscle sodium channels expressed in a mammalian cell line.
Analysis of steady state channel availability curves revealed two distinct effects of pentobarbital on both channel isoforms, i.e., a voltage-independent current reduction and an additional hyperpolarizing shift in the voltage dependence of channel availability, consistent with a preferential interaction with the inactivated channel state.
Propofol analogues. Synthesis, relationships between structure and affinity at GABAA receptor in rat brain, and differential electrophysiological profile at recombinant human GABAA receptors.
It is demonstrated that ligands displaying high affinity (i.e., 2-4, and 8) are able to increase GABA-stimulated chloride currents in oocytes expressing human GABAA receptors and to directly activate chloride channels in an electrophysiological assay.
Modulation of Cardiac Calcium Channels by Propofol
It is suggested that propofol may inhibit cardiac L‐type calcium current by interacting with the dihydropyridine‐binding site and increasing the apparent dissociation constant for [sup 3 H]nitrendipine without affecting binding‐site density.
Structural requirements for voltage‐dependent block of muscle sodium channels by phenol derivatives
All the phenol derivatives that are examined are effective blockers of skeletal muscle sodium channels, especially in conditions that are associated with membrane depolarization.
Mechanism for Bupivacaine Depression of Cardiac Conduction: Fast Block of Sodium Channels during the Action Potential with Slow Recovery from Block during Diastole
The results provide a possible explanation for the clinical observation that when bupivacaine accidently gains access to the general circulation, cardiac conduction can be depressed seriously and such depression may be difficult to reverse.
Central Nervous System Sodium Channels Are Significantly Suppressed at Clinical Concentrations of Volatile Anesthetics
Contrary to the hypothesis that sodium channels are insensitive to general anesthetics, the results presented here indicate that current through central nervous system sodium channels examined at physiologic membrane potentials is significantly blocked by clinical concentrations of volatileanesthetics.