• DOI:10.1213/00000539-200202000-00017
• Corpus ID: 34126217

The Inhibition of the N-Methyl-d-Aspartate Receptor Channel by Local Anesthetics in Mouse CA1 Pyramidal Neurons

@article{Nishizawa2002TheIO,
  title={The Inhibition of the N-Methyl-d-Aspartate Receptor Channel by Local Anesthetics in Mouse CA1 Pyramidal Neurons},
  author={Nobuyasu Nishizawa and Tetsuya Shirasaki and Shin‐ichi Nakao and Hiroko Matsuda and Koh Shingu},
  journal={Anesthesia \& Analgesia},
  year={2002},
  volume={94},
  pages={325-330}
}

• Nobuyasu Nishizawa, T. Shirasaki, +2 authors K. Shingu
• Published 1 February 2002
• Biology
• Anesthesia & Analgesia

Although the effects of local anesthetics on sodium channels and various other channels and receptors have been intensively investigated, there is little information available about their effects on N-methyl-d-aspartate (NMDA) receptors. We examined the effects of four local anesthetics (procaine, tetracaine, bupivacaine, and lidocaine) on NMDA-induced currents by using a whole-cell patch-clamp technique in dissociated mouse hippocampal pyramidal neurons. Procaine and tetracaine produced a reversible and concentration-dependent inhibition of NMDA-induced currents, but lidocaine showed little inhibition at 1 mM or less. The half-maximal inhibition values (mM; mean ± sem) for procaine, tetracaine, bupivacaine, and lidocaine at −60 mV were 0.296 ± 0.031, 0.637 ± 0.044, 2.781 ± 0.940 (extrapolated data), and 7.766 ± 14.093 (extrapolated data), respectively. Procaine 0.2 mM reduced the maximal NMDA-induced currents without affecting the 50% effective concentration values for NMDA. The inhibition by procaine exhibited voltage dependence and was more effective at negative potentials. These results indicate a noncompetitive antagonism of procaine on NMDA receptors and suggest that the inhibition is the result of a channel-blocking mechanism.