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

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Nishizawa N, Shirasaki T, Nakao S, Matsuda H, Shingu K

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

Anesth Analg. 2002 Feb;94(2):325-30, table of contents.

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11812692 [ View in PubMed

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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. 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Procaine	Glutamate receptor ionotropic, NMDA 3A	Protein	Humans	Yes	Antagonist	Details