Potentiation of gamma-aminobutyric acidA receptor Cl- current correlates with in vivo anesthetic potency.
Ten general anesthetics of varying structure and potency were investigated for possible modulatory effects on gamma-aminobutyric acid, (GABAA) receptors, using the voltage clamp technique. All 10 anesthetics studied were observed to prolong the duration of responses to exogenously applied GABA recorded in cultured rat hippocampal neurons. These modulatory effects of the anesthetics occurred at pharmacologically relevant concentrations. An excellent correlation exists between drug potency as modulators of the GABAA receptor and anesthetic potency in vivo. These data suggest an alternative interpretation of the historical association between anesthetic potency and lipophilicity. It is proposed that hydrophobic binding sites on ligand-gated ion channel proteins, such as the GABAA receptors, constitute a molecular target site for many general anesthetics.
Zimmerman
S A
SA
Department of Anesthesia and Critical Care, University of Chicago, Illinois.
Jones
M V
MV
Harrison
N L
NL
D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology; D002725:Chloroform / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D015640:Ion Channel Gating; D009474:Neurons / Q000187:drug effects; D051381:Rats; D018079:Receptors, GABA / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018681:Anesthetics, General; D018118:Chloride Channels; D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D002725:Chloroform