The inhibition of the N-methyl-D-aspartate receptor channel by local anesthetics in mouse CA1 pyramidal neurons.
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.


CONCLUSIONS
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.
Nishizawa
Nobuyasu
N
Department of Anesthesiology, Kansai Medical University, Moriguchi-City, Osaka, Japan.
Shirasaki
Tetsuya
T
Nakao
Shinichi
S
Matsuda
Hiroko
H
Shingu
Koh
K
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008012:Lidocaine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011343:Procaine / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D013748:Tetracaine / Q000494:pharmacology
D000779:Anesthetics, Local; D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D013748:Tetracaine; D011343:Procaine; D008012:Lidocaine; D002045:Bupivacaine