How theories evolved concerning the mechanism of action of barbiturates

@article{Lscher2012HowTE,
  title={How theories evolved concerning the mechanism of action of barbiturates},
  author={Wolfgang L{\"o}scher and Michael A. Rogawski},
  journal={Epilepsia},
  year={2012},
  volume={53}
}
The barbiturate phenobarbital has been in use in the treatment of epilepsy for 100 years. It has long been recognized that barbiturates act by prolonging and potentiating the action of γ‐aminobutyric acid (GABA) on GABAA receptors and at higher concentrations directly activating the receptors. A large body of data supports the concept that GABAA receptors are the primary central nervous system target for barbiturates, including the finding that transgenic mice with a point mutation in the β3… 
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TLDR
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Results from recent randomized controlled clinical trials with cenobamate suggest that this newest antiseizure alkyl‐carbamate possesses a degree of efficacy not witnessed since felbamate was approved in 1993, and it is not clear whether this impressive efficacy reflects an as yet undescribed mechanism of action or whether it possesses a unique synergy between its actions at the GABAA receptor and on persistent Na+ currents.
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  • R. Olsen, Guodong Li
  • Medicine
    Canadian journal of anaesthesia = Journal canadien d'anesthesie
  • 2011
TLDR
Establishment of a coherent and consistent structural model of the GABAA-R lends support to the conclusion that general anesthetics can modulate function by binding to appropriate domains on the protein.
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