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ANESTHETIC PHARMACOLOGY

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

Nobuyasu Nishizawa, MD^*, Tetsuya Shirasaki, PhD, Shinichi Nakao, MD, PhD^*, Hiroko Matsuda, MD, PhD, and Koh Shingu, MD, PhD^*

Departments of *Anesthesiology and Physiology, Kansai Medical University, Moriguchi-City, Osaka, Japan

Address correspondence and reprint requests to Shinichi Nakao, Department of Anesthesiology, Kansai Medical University, Moriguchi, Osaka 570-8507, Japan. Address e-mail to nakaos{at}takii.kmu.ac.jp

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.

IMPLICATIONS: 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. Both procaine and tetracaine produced a reversible and concentration-dependent inhibition of the NMDA-induced currents.

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