Ethanol and the NMDA Receptor: Insights into Ethanol Pharmacology

  • Boris Tabakoff
  • Carolyn S. Rabe
  • Kathleen A. Grant
  • Peter Valverius
  • Michael Hudspith
  • Paula J. Hoffman


The relationship between lipid solubility and the pharmacological actions of ethanol and other alcohols was demonstrated many years ago (Meyer and Gottlieb, 1926). Since then it has been shown that alcohols can partition into cell membranes and perturb the structure of the bulk membrane lipids (Chin and Goldstein, 1977), and that the intoxicating potency of alcohols is positively correlated with their lipid-perturbing capacity (Lyon et al., 1981). These results led to the hypothesis that the pharmacological actions of ethanol stem from its nonspecific effects on membrane lipid “fluidity” and subsequently a perturbation of the activities of membrane-bound proteins (e.g., receptors, enzymes). However, relatively high concentrations of ethanol are necessary to produce significant increases in membrane lipid fluidity (Chin and Goldstein, 1977; Lyon et al., 1981), and inspection of the literature reveals that the function of few membrane-bound proteins is significantly affected by concentrations of ethanol that are relevant in vivo. There are some exceptions to this observation, including the effects of low concentrations of ethanol on the stimulatory guanine nucleotide binding protein, Gs (Saito et al., 1985; Valverius et al., 1987), and the GABA receptor-coupled chloride channel (Allan and Harris, 1987; Suzdak et al., 1986), which is the major inhibitory neurotransmitter system in the brain.


NMDA Receptor Cerebellar Granule Cell Ethanol Withdrawal Striatal Slice Chronic Ethanol Ingestion 
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Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Boris Tabakoff
  • Carolyn S. Rabe
  • Kathleen A. Grant
  • Peter Valverius
  • Michael Hudspith
  • Paula J. Hoffman

There are no affiliations available

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