2, 6 di-tert-butylphenol, a nonanesthetic propofol analog, modulates α1β glycine receptor function in a manner distinct from propofol

J Ahrens, G Haeseler, M Leuwer… - Anesthesia & …, 2004 - journals.lww.com
J Ahrens, G Haeseler, M Leuwer, B Mohammadi, K Krampfl, R Dengler, J Bufler
Anesthesia & Analgesia, 2004journals.lww.com
IMPLICATIONS: This in vitro study shows that, at the glycine receptor level, propofol does
not differ from its nonanesthetic structural analog 2, 6 di-tert-butylphenol in its ability to
enhance the effect of small glycine concentrations but differs in its potential to directly
activate chloride inward currents in the absence of the natural agonist. Like most other
anesthetics, propofol acts on different molecular targets at different levels of the central
nervous system (1). The effects comprise positive allosteric modulation of inhibitory …
IMPLICATIONS: This in vitro study shows that, at the glycine receptor level, propofol does not differ from its nonanesthetic structural analog 2, 6 di-tert-butylphenol in its ability to enhance the effect of small glycine concentrations but differs in its potential to directly activate chloride inward currents in the absence of the natural agonist.
Like most other anesthetics, propofol acts on different molecular targets at different levels of the central nervous system (1). The effects comprise positive allosteric modulation of inhibitory synapses (2, 3) and blockade of voltage-operated sodium channels (4). Whereas gamma-aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in the brain, glycine plays a major role in the spinal cord and lower brainstem. Both GABA A and glycine receptors inhibit neuronal firing by opening chloride channels after agonist binding (5). The in vitro propofol effects on neocortical tissue are mediated almost exclusively via the GABA A receptor (6). There is experimental evidence that anesthetic-induced immobility, a cardinal aspect of general anesthesia, is produced—in the case of propofol, at least partly—by action on the spinal cord (7). Depression of spinal α-motoneuron excitability (8, 9) and depression of low-threshold sensory information processing within the spinal cord (10) have been shown during propofol anesthesia. However, in one study, this effect was observed only with very large propofol concentrations (11). Most spontaneous inhibitory postsynaptic currents in motor neurons are mediated by glycine receptors (12). The potential contribution of positive allo-steric modulation of spinal glycine receptors in propofol anesthesia is currently under discussion (13).
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