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

被引:16
作者
Ebert, B
Andersen, S
Hjeds, H
Dickenson, AH
机构
[1] Royal Danish Sch Pharm, Dept Pharmacol, DK-2100 Copenhagen, Denmark
[2] Royal Danish Sch Pharm, Pharmabiotec Res Ctr, DK-2100 Copenhagen, Denmark
[3] Royal Danish Sch Pharm, Dept Med Chem, DK-2100 Copenhagen, Denmark
[4] Amtssygehuset Roskilde, Dept Anaesthesiol, Roskilde, Denmark
[5] Amtssygehuset Roskilde, Pain Ctr, Roskilde, Denmark
[6] UCL, Dept Pharmacol, London, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
dextropropoxyphene; NMDA antagonist; opioids; neuropathic pain; noncompetitive;
D O I
10.1016/S0885-3924(98)00015-3
中图分类号
R19 [保健组织与事业(卫生事业管理)];
学科分类号
摘要
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.
引用
收藏
页码:269 / 274
页数:6
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