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Low Concentrations of Procaine and Diethylaminoethanol Reduce the Excitability but Not the Action Potential Amplitude of Hippocampal Pyramidal Cells

Butterworth John F. MD; Cole, Lisa R. BA
Anesthesia & Analgesia: October 1990

To determine whether concentrations of diethylaminoethanol (DEAE) and procaine below those that reduce the amplitude of action potentials might alter the excitability of brain cells, a single microelectrode intracellular recording technique was used to measure firing threshold and action potential amplitude of pyramidal cells in rat hippocampal slices. At low concentrations of both DEAE (≥5 mM) and procaine (≥0.5 mM), firing threshold was significantly increased (P < 0.01), whereas action potential spike amplitude was minimally altered. At higher concentrations, both drugs significantly decreased action potential spike amplitude (P < 0.025) as well as increased firing threshold (P < 0.001). Diethylaminoethanol tended to increase threshold relatively more than procaine, when drug concentrations that similarly reduced action potential amplitude were compared. All actions of DEAE and procaine were reversible. Inhibition of action potentials by DEAE and procaine was clearly concentration-dependent (P ≥ 0.015). Diethylaminoethanol effects on threshold were marginally concentration-dependent (P = 0.08); procaine did not demonstrate clear concentration-dependent effects (P = 0.33) over the concentrations tested in this study. These similar actions of procaine and DEAE on brain cells suggest a mechanism by which intravenous local anesthetics may contribute to the general anesthetic state. Moreover, it appears possible that procaine metabolism and DEAE accumulation may underlie the prolonged effects sometimes seen after intravenous procaine administration.

Address correspondence to Dr. Butterworth, Department of Anesthesia, Wake Forest University Medical Center, 300 South Hawthorne Road, Winston-Salem, NC 27103.

© 1990 International Anesthesia Research Society