title: The inhibition of the N-methyl-D-aspartate receptor channel by local anesthetics in mouse CA1 pyramidal neurons.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Kansai Medical University, Moriguchi-City, Osaka, Japan.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Nishizawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shirasaki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakao
authors.forename: Hiroko
authors.initials: H
authors.lastname: Matsuda
authors.forename: Koh
authors.initials: K
authors.lastname: Shingu
mesh_terms: 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
chemical_list: D000779:Anesthetics, Local; D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D013748:Tetracaine; D011343:Procaine; D008012:Lidocaine; D002045:Bupivacaine