Dextropropoxyphene acts as a noncompetitive N-methyl-D-aspartate antagonist

In order to elucidate whether opioid analgesics available on the Scandinavian market also act as noncompetitive N-methyl-D-aspartate (NMDA) antagonists, a series of commercially available opioids were screened for their affinity in [H-3](RS)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cycloheptene-5,10-imine ([H-3]MK-801) binding assay and potential inhibitory actions on responses to NMDA in the rat cortical wedge preparation. Of the screened compounds (codeine, dextropropoxyphene, etorphine, fentanyl, and morphine), only dextropropoxyphene, with an IC50 value in [H-3]MK-801 binding of 5 mu M, was found to be active. Further characterization of the interaction of dextropropoxyphene with the NMDA response in the rat cortical wedge preparation illustrated the noncompetitive NMDA antagonist activity of dextropropoxyphene. Analysis of the dextropropoxyphene inhibition curve of NMDA gave an IC50 value of 190 mu M and a Hill slope of 0.8. (C) U.S. Cancer Pain Relief Committee, 1998.