N-methyl-D-aspartate receptor channel block by meperidine is dependent on extracellular pH.

Article Details

Citation

Yamakura T, Sakimura K, Shimoji K

N-methyl-D-aspartate receptor channel block by meperidine is dependent on extracellular pH.

Anesth Analg. 2000 Apr;90(4):928-32.

PubMed ID
10735801 [ View in PubMed
]
Abstract

Large concentrations of meperidine inhibit N-methyl-D-aspartate-(NMDA) receptor channels by channel block mechanisms. Extracellular pH regulates the activity and drug sensitivity of NMDA-receptor channels. We examined the influence of extracellular pH on sensitivity to meperidine of epsilon/zeta heteromeric NMDA-receptor channels expressed in Xenopus oocytes. Inhibition of epsilon1/zeta1, epsilon2/zeta1, epsilon3/zeta1, and epsilon4/zeta1 channels by meperidine was dependent on pH, with more inhibition at acidic pH and less inhibition at alkaline pH. The degree of voltage-dependence of meperidine block was only slightly affected by changes in pH, whereas affinity for meperidine was greatly reduced at alkaline pH. Furthermore, interaction of meperidine with Mg(2+) block was reduced at alkaline pH. Because the percentage of the protonated form of meperidine is only slightly affected by pH, changes in properties of the meperidine binding site may be involved in mechanisms of alteration of meperidine potency by pH. IMPLICATIONS: At acidic pH the potency of meperidine for N-methyl-D-aspartate-receptor channels was increased. Any antinociceptive and neuroprotective benefit from the N-methyl-D-aspartate-receptor antagonist property of meperidine may be pH dependent.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
MeperidineGlutamate receptor ionotropic, NMDA 1ProteinHumans
Unknown
Antagonist
Details
MeperidineGlutamate receptor ionotropic, NMDA 2AProteinHumans
Unknown
Antagonist
Details
MeperidineGlutamate receptor ionotropic, NMDA 2BProteinHumans
Unknown
Antagonist
Details
MeperidineGlutamate receptor ionotropic, NMDA 2CProteinHumans
Unknown
Antagonist
Details
MeperidineGlutamate receptor ionotropic, NMDA 2DProteinHumans
Unknown
Antagonist
Details