DEXTROPROPOXYPHENE ACTS AS A NONCOMPETITIVE N-METHYL-D-ASPARTATE ANTAGONIST

In order to elucidate whether opioid analgesics available on the Scand inavian 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 inh ibitory actions on responses to NMDA in the rat cortical wedge prepara tion. Of the screened compounds (codeine, dextropropoxyphene, etorphin e, fentanyl, and morphine), only dextropropoxyphene, with an IC50 valu e in [H-3]MK-801 binding of 5 mu M, was found to be active. Further ch aracterization of the interaction of dextropropoxyphene with the NMDA response in the rat cortical wedge preparation illustrated the noncomp etitive NMDA antagonist activity of dextropropoxyphene. Analysis of th e dextropropoxyphene inhibition curve of NMDA gave an IC50 value of 19 0 mu M and a Hill slope of 0.8. (C) U.S. Cancer Pain Relief Committee, 1998.